The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is ...The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.展开更多
Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control...Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.展开更多
Background: Spontaneously ruptured hepatocellular carcinoma(rHCC) is a life-threatening condition. Transarterial chemoembolization(TACE) is a widely accepted treatment;however, it can lead to serious complications,esp...Background: Spontaneously ruptured hepatocellular carcinoma(rHCC) is a life-threatening condition. Transarterial chemoembolization(TACE) is a widely accepted treatment;however, it can lead to serious complications,especially liver failure. We sought to identify preoperative predictors of liver failure in patients with rHCC undergoing TACE.Methods: Patients with rHCC who received TACE as the initial therapy were retrospectively studied at our institution between January 2016 and December 2021. Based on the occurrence of liver failure after TACE, the patients were divided into liver failure and no-liver failure groups. Predictors of liver failure after TACE were analyzed using univariate and multivariate regression analyses. The predictive performance was assessed using the area under the curve(AUC). Delong’s test was used to compare predictive efficiency.Results: Sixty patients(19 and 41 in the liver failure and non-liver failure groups, respectively) were included.Multivariate analysis showed that preoperative prothrombin activity(PTA) level(odds ratio [OR], 0.956;95%confidence interval [CI], 0.920–0.994;P = 0.024) and Child-Pugh grade B(OR, 6.419;95% CI, 1.123–36.677;P= 0.037) were independent predictors of liver failure after TACE in patients with rHCC. The AUCs of the preoperative PTA levels and Child-Pugh grade B for predicting liver failure after TACE in patients with rHCC were0.783 and 0.764, respectively.Conclusion: Preoperative PTA level and Child-Pugh grade B were significant independent risk factors for liver failure after TACE in patients with rHCC. These can be used to predict liver failure after TACE in patients with rHCC for individual decision-making regarding treatment planning.展开更多
Background: Probable benign paroxysmal positional vertigo, spontaneously resolved (pBPPVsr), is a variant of benign paroxysmal positional vertigo (BPPV) in which there is no observable nystagmus and no vertigo with an...Background: Probable benign paroxysmal positional vertigo, spontaneously resolved (pBPPVsr), is a variant of benign paroxysmal positional vertigo (BPPV) in which there is no observable nystagmus and no vertigo with any positional maneuver. Objectives: To calculate the incidence pBPPVsr, compare the characteristics of the patients with pBPPVsr and BPPV not spontaneously resolved and describe the spontaneous resolution in the natural course of BPPV. Methods: Multicenter prospective descriptive study. During a one-year period, all patients with suspected BPPV that presented to the Neurotology Units of five participating centers were recruited. The incidence of pBPPVsr was calculated as a percentage of the total number of patients with BPPV. The prevalence of several variables was compared between pBPPVsr and BPPV not spontaneously resolved. The timing of spontaneous resolution was estimated using Kaplan-Meier curves. Results: 457 patients met the inclusion criteria. The incidence of pBPPVsr was 33.5%. It was significantly higher in males, in patients with normal bone mass and in patients who were not taking sulpiride. A rate of 18% of spontaneous resolution after the first month and 51% after the first year was found. This percentage did not change in a significant way after this moment. The curves for males, patients under 50 and patients with normal blood pressure decreased significantly faster. Conclusions: In our serie, BPPV spontaneously resolved in half of the patients with BPPV during the first year. This seemed to occur more commonly in males and could have been hindered by sulpiride intake, osteoporosis, advanced age and high blood pressure.展开更多
To observe the effects of different acupuncture manipulations on blood pressure and target organ damage in spontaneously hypertensive rats(SHRs), this study used the reinforcing twirling method(1.5–2-mm depth; rotati...To observe the effects of different acupuncture manipulations on blood pressure and target organ damage in spontaneously hypertensive rats(SHRs), this study used the reinforcing twirling method(1.5–2-mm depth; rotating needle clockwise for 360° and then counter clockwise for 360°, with the thumb moving heavily forward and gently backward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), the reducing twirling method(1.5–2-mm depth; rotating needle counter clockwise for 360° and then clockwise for 360°, with the thumb moving heavily backward and gently forward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), and the needle retaining method(1.5–2-mm depth and retaining the needle for 10 minutes). Bilateral Taichong(LR3) was treated by acupuncture using different manipulations and manual stimulation. Reinforcing twirling, reducing twirling, and needle retaining resulted in a decreased number of apoptotic cells, reduced Bax m RNA and protein expression, and an increased Bcl-2/Bax ratio in the hippocampus compared with the SHR group. Among these groups, the Bcl-2/Bax protein ratio was highest in the reducing twirling group, and the Bcl-2/Bax m RNA ratio was highest in the needle retaining group. These results suggest that reinforcing twirling, reducing twirling, and needle retaining methods all improve blood pressure and prevent target organ damage by increasing the hippocampal Bcl-2/Bax ratio and inhibiting cell apoptosis in the hippocampus in SHR.展开更多
Peptide hydrolysates of silkworm pupae protein with molecular weight of less than 5000 Da were prepared by ultrafiltration. The extracted peptide hydrolysates of silkworm pupae protein had inhibitory action on angiote...Peptide hydrolysates of silkworm pupae protein with molecular weight of less than 5000 Da were prepared by ultrafiltration. The extracted peptide hydrolysates of silkworm pupae protein had inhibitory action on angiotensin-I-converting enzyme activity in vitro. The hydrolysates were orally administered to spontaneously hypertensive rats (SHR) in one period and long-term (four weeks). The results showed that the systolic blood pressure (SBP) of the treatment groups decreased in a dose-related manner. After one oral administration of silkworm protein hydrolysates with doses of 60, 20 and 5 mg/kg, the SBP of SHR decreased by 21.5, 13.8, and 9.0 mmHg in 1.5 h. After four weeks of the treatment in 80 mg/kg, the SBP decreased by 25 mmHg, with the antihypertensive activity close to 4 mg/kg of captopril;the SBP of the 40 mg/kg dose group also decreased by 17.5 mmHg. The peptide hydrolysate did not affect the SBP in normal, non-hypertensive rats in one period and long-term treatments. The acute toxicity research showed that the peptide hydrolysates were safe and without side effects. This research would be helpful in exploring the silkworm protein peptides as functional components for the antihypertension treatment.展开更多
The effects of salvia miltiorrhiza Bge (SMB) on left ventricular hypertrophy (LVH) and the expression of tumor necrosis factor-α (TNF-α) in the left ventricle of spontaneously hypertensive rats and the action mechan...The effects of salvia miltiorrhiza Bge (SMB) on left ventricular hypertrophy (LVH) and the expression of tumor necrosis factor-α (TNF-α) in the left ventricle of spontaneously hypertensive rats and the action mechanism were investigated. Normal Wistar-kyoto (WKY) rats were used as negative control, and spontaneously hypertensive rats (SHR) were randomly assigned to receive pla- cebo or SMB. SMB (1 g/kg·d) was injected intraperitoneally for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured. HE, VG and immunohistochemical staining combined with computed morphometry were employed to evaluate the cardiomyocyte size, diameter, the collagen volume fraction (CVF), perivascular circumferential area (PVCA), and tumor necrosis factor-α (TNF-α) expression in the left ventricular tissue. The results showed, as compared with WKY rats, the SBP, LVMI, cardiomyocyte size, diameter, CVF, PCVA, and TNF-α expression were increased markedly in the 20-week-old spontaneously hypertensive rats. SMB decreased LVMI (P<0.01), size of cardiomyocytes (P<0.01), collagen volume fraction (P<0.01), perivascular circum- ferential area (P<0.01), and TNF-α expression (P<0.01), but had no effect on SBP (P>0.05). It was suggested that chronic administration of SMB could inhibit and reverse the development of LVH in spontaneously hypertensive rats independent of BP. TNF-α may be involved in the reversal mecha- nism of LVH by SMB.展开更多
OBJECTIVE To explore the underlying mechanisms involved in the effect of sesamin on aortic NO bioactivity in spontaneously hypertensive rat(SHR).METHODS Sesamin was orally administered for consecutive 8 weeks in SHR.S...OBJECTIVE To explore the underlying mechanisms involved in the effect of sesamin on aortic NO bioactivity in spontaneously hypertensive rat(SHR).METHODS Sesamin was orally administered for consecutive 8 weeks in SHR.Systolic blood pressure(SBP)was measured using the tail-cuff method.The aortas were isolated and in vitro vascular reactivity studies were performed.Superoxide anion production in carotid arteries was assessed by dihydroethidium fluorescence staining.The protein expression of endothelial nitric oxide synthase(eNOS),phosphorylated eNOS(P-eNOS),dihydrofolate reductase(DHFR),nicotinamide adenine dinucleotide phosphate(NADPH)oxidase subunit p47 phox and copper,zinc-superoxide dismutase(Cu/Zn-SOD)in aortas was detected by Western blotting.The dimeric form of eNOS in aortas was determined by low-temperature SDS-PAGE.Aortic level of nitrotyrosine and activities of antioxidant enzymes,namely,total SOD(T-SOD),glutathione peroxidase(GPx)and catalase were also detected.RESULTS In SHR,sesamin treatment reduced SBP,improved vascular relaxation induced by acetylcholine and enhanced aortic NO bioactivity.Sesamin treatment enhanced NO biosynthesis in SHR aortas was due to upregulated P-eNOS and suppressed eNOS uncoupling,and the latter effect might be attributed to decreased nitrotyrosine and upregulated DHFR.Sesamin also reducd the NO oxidative inactivation and decreased the superoxide anion production through downregulation of p47 phox and amelioration of eNOS uncoupling.In addition,sesamin treatment did not alter the levels of GPx and catalase activity but obviously reduced the compensatory elevated T-SOD activity and Cu/Zn-SOD protein expression.CONCLUSION Chronic treatment with sesamin could reduce hypertension and improve endothelial dysfunction through enhancement of NO bioactivity in SHRs aortas.展开更多
Taurine(2-aminoethanesulfonic acid) is a β-amino acid found in many tissues particularly brain, myocardium, and kidney. It plays several physiological roles including cardiac contraction, antioxidation, and blunting ...Taurine(2-aminoethanesulfonic acid) is a β-amino acid found in many tissues particularly brain, myocardium, and kidney. It plays several physiological roles including cardiac contraction, antioxidation, and blunting of hypertension. Though several lines of evidence indicate that dietary taurine can reduce hypertension in humans and in animal models, evidence that taurine supplementation reduces hypertension in humans has not been conclusive. One reason for the inconclusive nature of past studies may be that taurine having both positive and negative effects on cardiovascular system depending on when it is assessed, some effects may occur early, while others only appear later. Further, other consideration may play a role, e.g., taurine supplementation improves hypertension in spontaneously hypertensive rats on a low salt diet but fails to attenuate hypertension on a high salt diet. In humans, some epidemiologic studies indicate that people with high taurine and low salt diets display lower arterial pressure than those with low taurine and high salt diets. Differences in techniques for measuring arterial pressure, duration of treatment, and animal models likely affect the response in different studies. This review considers both the positive and negative effects of taurine on blood pressure in animal models and their applications for human interventions.展开更多
The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis ...The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis in hypertensive nephropathy are not fully understood.In the present study,we investigated the correlation of epithelium-like cells with glomerular injury,and the effects of early drug intervention with telmisartan,an anti-hypertensive drug,on the growth of epithelium-like cells.The results showed that the epithelium-like cells were obviously observed lining along the luminal surface of Bowman’s capsule in glomeruli,significantly resulting in the atrophy of the glomerular tuft.Some of the epithelium-like cells strongly expressed proliferating cell nuclear antigen(PCNA)and vimentin,indicating active cellular proliferation.The incidence of epithelium-like cells varied from 13.6%to 54.4%of glomeruli in 48-week-old SHRs,and from 5.1%to 18.0%of glomeruli in age-matched Wistar-Kyoto(WKY)rats(P<0.01).The linear regression analysis further confirmed an obvious correlation between the incidence of epithelium-like cells and the glomerular injury.Moreover,early intervention with telmisartan could dramatically attenuate the progression of epithelium-like cells growth.However,no significant effect of telmisartan on the established epithelium-like cells was observed.Taken together,we demonstrated the involvement of abnormal epithelium-like cells growth in glomerular injury during hypertensive nephropathy in SHRs,and firstly showed the positive effects of the anti-hypertensive drug on the progression of epithelium-like cells growth.展开更多
Some citrus flavonoids have been reported to possess antioxidant activities that moderate endothelial dysfunction and show protective effects on cardiovascular disease. We have investigated the protective effects of n...Some citrus flavonoids have been reported to possess antioxidant activities that moderate endothelial dysfunction and show protective effects on cardiovascular disease. We have investigated the protective effects of nobiletin (5,6,7,8,3’,4’-hexamethoxy flavone) derived from the peel of Citrus depressa Hayata (Shiikuwasha), a citrus fruit produced in Okinawa prefecture in Japan on hypertension and thrombogenicity in cerebral vessels of stroke-prone spontaneously hypertensive rats (SHRSP). Nobiletin was added to the diet of male SHRSP (7 weeks old) for 4 weeks. The age-related increase in systolic blood pressure usually observed in SHRSP was significantly suppressed in the treated animals. Thrombogenesis in pial blood vessels, determined using a He-Ne laser technique, and antioxidant activity, assessed by measuring urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG), were significantly reduced after treatment. Urinary nitric oxide (NO) metabolites and acetylcholine-induced endothelial relaxation were increased after dietary intervention. These results strongly suggested that antihypertensive and antithrombotic effects of nobiletin may be related to an increase in bioavailable NO, possibly mediated by the scavenging of reactive oxygen species (ROS).展开更多
Objective:To investigate the expression of phosphorylated peroxisome proliferators-activated receptor y(p-PPARY) in the aging thoracic aorta of spontaneously hypertensive rat(SHR) and the inhibitory effect of rosiglit...Objective:To investigate the expression of phosphorylated peroxisome proliferators-activated receptor y(p-PPARY) in the aging thoracic aorta of spontaneously hypertensive rat(SHR) and the inhibitory effect of rosiglitazone on the phosphorylation of PPART.Methods:16,32 and 64 week-old Wistar-Kyoto rats(WKY) and SHR were randomly and respectively divided into WKY,SHR and SHR+rosiglitazone group(9 in each group).The rats in SHR+rosiglitazone group were treated with rosiglitazone(5 mg/kg,intragastrically) for 56 d,whereas normal saline was applied in WKY and SHR groups.Systolic blood pressure(SBP)of rats was measured by tail cuff method.Histopathological damage of thoracic aorta was analyzed using Hematoxylin-Eosin(HE) staining.Immunohistochemical staining and western blot were performed to test the level of p-PPARY protein in the thoracic aorta arising from each group.Results:The SBP in 16,32 and 64 week-old SHR were significantly higher as compared with those in matched WKY rats(P<0.05,respectively).HE staining showed increased content of smooth muscle cell,wrinkled lining endothelium and increased thickness of internal elastic lamina in the thoracic aorta of SHR.Immunohistochemical staining and western blot indicated that the levels of p-PPARY in the thoracic aorta arising from SHR were obviously higher than those in the thoracic aorta arising from WKY rats(P<0.05,respectively).Importantly,the high SBP,histopathological abnormalities of the thoracic aorta and elevated p-PPARY expression were prominently abrogated by rosiglitazone treatment in SHR(P<0.05,respectively).Furthermore,the SBP,histopathological abnormalities of the thoracic aorta and p-PPARY expression were positively correlated with age in SHR(P<0.05,respectively).Conclusions:The PPARY phosphorylation was observed in the thoracic aorta of SHR and its expression was increased by the increase of age.Furthermore,rosiglitazone inhibited the PPARY phosphorylation and suppressed vascular aging in SHR.展开更多
Objective:To investigate the effect of alpha-lipoic acid(ALA)supplementation on systolic blood pressure(SBP),renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats(SHR)and SHR administere...Objective:To investigate the effect of alpha-lipoic acid(ALA)supplementation on systolic blood pressure(SBP),renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats(SHR)and SHR administered with Nω-nitro-L-arginine methyl ester(L-NAME).Methods:Male rats were divided into four groups(SHR,SHR+ALA,SHR+L-NAME,SHR+ALA+L-NAME).The respective group of rats was administered with ALA(100 mg/kg/day)from age 4 weeks to 28 weeks and L-NAME(25 mg/kg/day)from age 16 weeks to 28 weeks.SBP was measured every two weeks and twenty four hour urine was collected at 4 weeks,16 weeks and 28 weeks for estimation of protein,creatinine and N-acetyl-e end of 28 weeks,rats were sacrificed and blood and kidneys colα-Dglucosaminidase.At thlected for assessment of blood creatinine,kidney thiobarbituric acid reactive substances,protein carbonyls,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,glutathione S-transferase,glutathione disulfide,glutathione,total antioxidant status and nitric oxide as well as histopathological examination.Results:ALA supplementation significantly reduced SBP of SHR and SHR+L-NAME rats when compared to their respective non-supplemented groups.Renal oxidant status markers including thiobarbituric acid reactive substances and protein carbonyls were significantly reduced on SHR and SHR+L-NAME rats supplemented with ALA at 28 weeks as well as ALA supplementation significantly increased renal antioxidants including superoxide dismutase,catalase,glutathione peroxidase,glutathione S-transferase,glutathione and glutathione/glutathione disulfide ratio at 28 weeks.No significant change in nitric oxide levels was observed between the ALA supplemented and non-supplemented groups.Renal dysfunction was ameliorated on ALA supplementation as evidenced by significant reduction in urine protein levels,N-acetyl-α-D-glucosaminidase activity and significant increase of creatinine clearance in SHR and SHR+L-NAME at 28 weeks.Renal histopathological examination showed that ALA supplementation prevented vascular damage in SHR and ameliorated glomerular damage in SHR+L-NAME at 28 weeks.Conclusions:ALA has hypotensive and renoprotective effects on both SHR and SHR+LNAME,which could be due to its ability to ameliorate oxidative stress in the kidneys.展开更多
Aim To study the activity and mechanism of inhibition of myocardial hypertrophy of total flavonoids of Cydonia oblonga Mill. in spontaneously hypertensive rats. Methods Total flavonoids of COM （COMF） were sepa- rate...Aim To study the activity and mechanism of inhibition of myocardial hypertrophy of total flavonoids of Cydonia oblonga Mill. in spontaneously hypertensive rats. Methods Total flavonoids of COM （COMF） were sepa- rated and purified by the optimal process. SHtl were divided into 6 groups： SHR control group （SHR） , captopril group （SHR ＋ CAP, 25 μg · g^-1）, Eucommia ulmoides Oliver group （SHR ＋ EUO, 30 μg · g^-1）, low （SHR ＋ COMF-L, 40 μg · g^-1） ,middle （SHR ＋ COMF-M, 80 μg· g^-1） and high dose （SHR ＋ COMF-H, 160 μg · g^-1） of COMF groups. Wistar-Kyoto （WKY） rats （n= 8 ） were given distilled water as control The drugs were given by intragastric administration for 16 weeks. The histological and pathological examination of the heart were performed and organic damage were valued. The levels of Ang II and ALD in blood and heart were evaluated. The mRNA and protein expression of ACE, ACE2 and AT~ was determined by RT-PCR and Western blot to evaluate the effect of COMF on RAAS. Results Compared with SHR control group, HW, HW/BW, LVM and LVM/BW de- creased in SHR ＋ COMF-M and SHR ＋ COMF-H groups; Cadiomyocyte hypertrophy was inhibited in COMF groups; The concentration of Ang 11 and ALD in heart and blood decreased; ACE and AT1 mRNA and protein ex- pression in heart tissue decreased while ACE2 mRNA expression increased （P 〈 0.01 or P 〈 0.05） , Conclusion Total flavonoids of Cydonia oblonga Mill. showed the effect of inhibition of myocardial hypertrophy in spontaneously hypertensive rats and the mechanism was related to. inhibit the activity of Renin-angiotensin-aldosterone system.展开更多
Objective To explore the effectiveness of renal denervation (RDN) on blood pressure with the appropriate dosage of phenol/ethanol solution in spontaneously hypertensive rats (SHRs). Methods RDN was performed on the bi...Objective To explore the effectiveness of renal denervation (RDN) on blood pressure with the appropriate dosage of phenol/ethanol solution in spontaneously hypertensive rats (SHRs). Methods RDN was performed on the bilateral renal artery. Forty SHRs were divided into four groups according on the dosage of phenol (10% phenol in absolute ethanol): sham group, 0.5 mL phenol group, 1 mL phenol group and 1.5 mL phenol group (n = 10 in each group). Blood pressure was measured by tail-cuff plethysmography. Plasma creatinine was determined four weeks after the treatment. The kidneys and renal arteries were collected and processed for histological examination. Results A sustained decrease in systolic blood pressure (SBP) was only observed after the application of 1 mL phenol for four weeks, while SBP was lowered during the first week after RDN and increased in the following three weeks in the 0.5 mL and 1.5 mL phenol groups compared with the sham group. Renal norepinephrine (NE) was significantly decreased four weeks after RDN in the 1 mL and 1.5 mL phenol group compared with the sham group, but not in the 0.5 ml group. RDN with 1 mL phenol obviously reduced glomerular fibrosis. Histopathological analysis showed that tyrosine hydroxylase immunoreactivity was lower in the 1 mL and 1.5 mL phenol groups compared with the sham group. Moderate renal artery damage occurred in the 1.5 mL phenol group. Conclusion Chemical denervation with 1 ml phenol (10% phenol in absolute ethanol) effectively and safely damaged peripheral renal sympathetic nerves and contributed to the sustained reduction of blood pressure in SHRs.展开更多
AIM: To investigate the alterations in both structure and contractile responsiveness of ocular ciliary artery(OCA) in spontaneously hypertensive rat(SHR).METHODS: In this experiment, 20-week-old male SHR and Wistar Ky...AIM: To investigate the alterations in both structure and contractile responsiveness of ocular ciliary artery(OCA) in spontaneously hypertensive rat(SHR).METHODS: In this experiment, 20-week-old male SHR and Wistar Kyoto rat(WKY) were studied. The heart rate(HR), the blood pressure(BP; the systolic BP and the diastolic BP) of rats with an electronic sphygmomanometer were measured. Vascular morphometry and isometric tension measurement were used to investigate the alterations in structure and contractility of OCA.RESULTS: A general narrowing of OCAs was observed in SHR compared to the control WYK. In SHR, the media of OCAs were thicker, the luminal diameters were smaller, and the media-to-lumen ratios were higher when compared with WKY(P<0.05). The contractions of OCAs evoked by norepinephrine were smaller in SHR compared to control(P<0.05). Then, OCAs were pretreated with iberiotoxin, L-NAME, or indomethacin 30 min before norepinephrineinduced contraction. Iberiotoxin(0.1 μmol/L) has not changed the norepinephrine-induced contractions in OCAs from both groups. However, L-NAME(100 μmol/L) increased the vasoconstrictions, the increased extents were similar in SHR and WKY(P>0.05). Indomethacin(10 μmol/L) decreased the contractions induced by norepinephrine in OCAs from WKY(P<0.05), but did not change those contractions in vessels from SHR(P>0.05).CONCLUSION: Our results demonstrate that the structure and function of OCAs are altered in hypertension. OCAs from SHR are remodeled with decreased lumen diameter and increased media-to-lumen ratio. Moreover, the contractile responsiveness of OCAs from SHR is diminished due to the disruption of vasoconstrictive effect of prostaglandins.展开更多
OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model ...OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model group(SHR,receive distilled water)and SF treatment groups(SF 20,40 and 80 mg·kg^-1 per day,respectively).Age-matched male Wistar-Kyoto(WKY)rats gavaged with distilled water served as controls.After 12 weeks of treatment,the effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement,pathological analysis and the expression of atrial natriuretic peptide(ANP),myosin heavy chainβ(β-MHC)-a gene related to myocardial hypertrophy.In order to explore the mechanism of SF on myocardial hypertrophy,the calcium-sensing receptor(CaSR),calcineurin(CaN),nuclear factor of activated T cell 3(NFAT3),phosphorylation NFAT3(p-NFAT3),zinc finger transcription factor(GATA4),phosphorylation GATA4(p-GATA4),protein kinase Cβ(PKC-β),Raf-1,extracellular regulated protein kinase 1/2(ERK 1/2),phosphorylation ERK1/2(p-ERK 1/2)and mitogen-activated protein kinase phosphatase-1(MKP-1)were detected.RESULTS The myocardial hypertrophy parameters,myocardial cell cross section area,left ventricular wall thickness and expression of ANP and β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 were significantly increased,while the left ventricular cavity was significantly smaller,expression of p-NFAT3 and MKP-1 were significantly decreased,meanwhile,the ultra⁃structure of cardiomyocytes was significantly damaged in 26-week-old SHR rats.Notably,SF significantly ameliorated myocardial hyper⁃trophy in 26-week-old SHR rats;suppressed the overexpression of ANP,β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 and increased the expression of p-NFAT3 and MKP-1.CONCLUSION SF can inhibit cardiac hypertrophy in SHR rats,and the mechanism may be related to the inhibition of CaSR mediated signaling pathway.展开更多
Objectives: 1) To reveal, among spontaneously hypertensive rats, subpopulations that diverge in attention to objects enriching an empty cross-maze;2) To evaluate effect of clinically efficient drug for treatment of at...Objectives: 1) To reveal, among spontaneously hypertensive rats, subpopulations that diverge in attention to objects enriching an empty cross-maze;2) To evaluate effect of clinically efficient drug for treatment of attention deficiency atomoxetine on the attention to environmental cues in attentionally-low rats. Method: A novel paradigm that provides measure of attention towards enriching objects independent of general locomotor activity and spatial orientation is employed. The apparatus consists of 4-arm radial maze, two arms of which contain objects (enriched compartments). Animals exploring the objects typically stay longer in enriched parts of maze than in empty arms and have a higher score of enrichment discrimination ratio. Results: Frequency distribution of the enrichment discrimination ratio had clear bimodal shape that differed significantly from normal distribution suggesting the existence of subpopulations of attentionally-low and -high individuals. The attentionally-low phenotype did not show inferiority in spatial orientation as compared with attentionally-high phenotype. The phenotypes did not differ from each other in measures of locomo- tor activity and blood pressure. Atomoxetine (3 mg/kg, orally, once daily for 4 days) enhanced enrichment discrimina- tion in animals of attentionally-low phenotype. Single administration of the drug was ineffective. Conclusion: Popula- tion of spontaneously hypertensive rat includes two phenotypes of attentionally-low and -high individuals. Subchronic atomoxetine ameliorates attention to environmental cues in attentionally-low rats. The enrichment discrimination test could be useful in studies of neurobiology of attention deficit condition and for screening of novel drug candidates.展开更多
Dietary γ-amino butyric acid (GABA) has been suggested to decrease systolic blood pressure. This study aimed to ex-amine the effects of dietary GABA on the life span of stroke-prone spontaneously hypertensive rats (S...Dietary γ-amino butyric acid (GABA) has been suggested to decrease systolic blood pressure. This study aimed to ex-amine the effects of dietary GABA on the life span of stroke-prone spontaneously hypertensive rats (SHRSPs). In this study, life span was determined for SHRSPs provided 1% NaCl solution or 0.01% GABA in 1% NaCl solution as drinking water. The life span of the GABA-fed group (76.3 ± 1.65 days) was significantly shorter than that of the control group (81.6 ± 0.88 days). The results of this study may not be applicable to humans. Future studies will be necessary to elucidate the mechanism underlying this phenomenon.展开更多
基金supported by the National Natural Science Foundation of China(No.31901635)。
文摘The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.
基金funded by the Universiti Tunku Abdul Rahman Research fund(IPSR/RMC/UTARRF/2019-C2/L08)。
文摘Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.
文摘Background: Spontaneously ruptured hepatocellular carcinoma(rHCC) is a life-threatening condition. Transarterial chemoembolization(TACE) is a widely accepted treatment;however, it can lead to serious complications,especially liver failure. We sought to identify preoperative predictors of liver failure in patients with rHCC undergoing TACE.Methods: Patients with rHCC who received TACE as the initial therapy were retrospectively studied at our institution between January 2016 and December 2021. Based on the occurrence of liver failure after TACE, the patients were divided into liver failure and no-liver failure groups. Predictors of liver failure after TACE were analyzed using univariate and multivariate regression analyses. The predictive performance was assessed using the area under the curve(AUC). Delong’s test was used to compare predictive efficiency.Results: Sixty patients(19 and 41 in the liver failure and non-liver failure groups, respectively) were included.Multivariate analysis showed that preoperative prothrombin activity(PTA) level(odds ratio [OR], 0.956;95%confidence interval [CI], 0.920–0.994;P = 0.024) and Child-Pugh grade B(OR, 6.419;95% CI, 1.123–36.677;P= 0.037) were independent predictors of liver failure after TACE in patients with rHCC. The AUCs of the preoperative PTA levels and Child-Pugh grade B for predicting liver failure after TACE in patients with rHCC were0.783 and 0.764, respectively.Conclusion: Preoperative PTA level and Child-Pugh grade B were significant independent risk factors for liver failure after TACE in patients with rHCC. These can be used to predict liver failure after TACE in patients with rHCC for individual decision-making regarding treatment planning.
文摘Background: Probable benign paroxysmal positional vertigo, spontaneously resolved (pBPPVsr), is a variant of benign paroxysmal positional vertigo (BPPV) in which there is no observable nystagmus and no vertigo with any positional maneuver. Objectives: To calculate the incidence pBPPVsr, compare the characteristics of the patients with pBPPVsr and BPPV not spontaneously resolved and describe the spontaneous resolution in the natural course of BPPV. Methods: Multicenter prospective descriptive study. During a one-year period, all patients with suspected BPPV that presented to the Neurotology Units of five participating centers were recruited. The incidence of pBPPVsr was calculated as a percentage of the total number of patients with BPPV. The prevalence of several variables was compared between pBPPVsr and BPPV not spontaneously resolved. The timing of spontaneous resolution was estimated using Kaplan-Meier curves. Results: 457 patients met the inclusion criteria. The incidence of pBPPVsr was 33.5%. It was significantly higher in males, in patients with normal bone mass and in patients who were not taking sulpiride. A rate of 18% of spontaneous resolution after the first month and 51% after the first year was found. This percentage did not change in a significant way after this moment. The curves for males, patients under 50 and patients with normal blood pressure decreased significantly faster. Conclusions: In our serie, BPPV spontaneously resolved in half of the patients with BPPV during the first year. This seemed to occur more commonly in males and could have been hindered by sulpiride intake, osteoporosis, advanced age and high blood pressure.
基金supported by the National Natural Science Foundation of China,No.81072861,81373727
文摘To observe the effects of different acupuncture manipulations on blood pressure and target organ damage in spontaneously hypertensive rats(SHRs), this study used the reinforcing twirling method(1.5–2-mm depth; rotating needle clockwise for 360° and then counter clockwise for 360°, with the thumb moving heavily forward and gently backward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), the reducing twirling method(1.5–2-mm depth; rotating needle counter clockwise for 360° and then clockwise for 360°, with the thumb moving heavily backward and gently forward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), and the needle retaining method(1.5–2-mm depth and retaining the needle for 10 minutes). Bilateral Taichong(LR3) was treated by acupuncture using different manipulations and manual stimulation. Reinforcing twirling, reducing twirling, and needle retaining resulted in a decreased number of apoptotic cells, reduced Bax m RNA and protein expression, and an increased Bcl-2/Bax ratio in the hippocampus compared with the SHR group. Among these groups, the Bcl-2/Bax protein ratio was highest in the reducing twirling group, and the Bcl-2/Bax m RNA ratio was highest in the needle retaining group. These results suggest that reinforcing twirling, reducing twirling, and needle retaining methods all improve blood pressure and prevent target organ damage by increasing the hippocampal Bcl-2/Bax ratio and inhibiting cell apoptosis in the hippocampus in SHR.
文摘Peptide hydrolysates of silkworm pupae protein with molecular weight of less than 5000 Da were prepared by ultrafiltration. The extracted peptide hydrolysates of silkworm pupae protein had inhibitory action on angiotensin-I-converting enzyme activity in vitro. The hydrolysates were orally administered to spontaneously hypertensive rats (SHR) in one period and long-term (four weeks). The results showed that the systolic blood pressure (SBP) of the treatment groups decreased in a dose-related manner. After one oral administration of silkworm protein hydrolysates with doses of 60, 20 and 5 mg/kg, the SBP of SHR decreased by 21.5, 13.8, and 9.0 mmHg in 1.5 h. After four weeks of the treatment in 80 mg/kg, the SBP decreased by 25 mmHg, with the antihypertensive activity close to 4 mg/kg of captopril;the SBP of the 40 mg/kg dose group also decreased by 17.5 mmHg. The peptide hydrolysate did not affect the SBP in normal, non-hypertensive rats in one period and long-term treatments. The acute toxicity research showed that the peptide hydrolysates were safe and without side effects. This research would be helpful in exploring the silkworm protein peptides as functional components for the antihypertension treatment.
文摘The effects of salvia miltiorrhiza Bge (SMB) on left ventricular hypertrophy (LVH) and the expression of tumor necrosis factor-α (TNF-α) in the left ventricle of spontaneously hypertensive rats and the action mechanism were investigated. Normal Wistar-kyoto (WKY) rats were used as negative control, and spontaneously hypertensive rats (SHR) were randomly assigned to receive pla- cebo or SMB. SMB (1 g/kg·d) was injected intraperitoneally for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured. HE, VG and immunohistochemical staining combined with computed morphometry were employed to evaluate the cardiomyocyte size, diameter, the collagen volume fraction (CVF), perivascular circumferential area (PVCA), and tumor necrosis factor-α (TNF-α) expression in the left ventricular tissue. The results showed, as compared with WKY rats, the SBP, LVMI, cardiomyocyte size, diameter, CVF, PCVA, and TNF-α expression were increased markedly in the 20-week-old spontaneously hypertensive rats. SMB decreased LVMI (P<0.01), size of cardiomyocytes (P<0.01), collagen volume fraction (P<0.01), perivascular circum- ferential area (P<0.01), and TNF-α expression (P<0.01), but had no effect on SBP (P>0.05). It was suggested that chronic administration of SMB could inhibit and reverse the development of LVH in spontaneously hypertensive rats independent of BP. TNF-α may be involved in the reversal mecha- nism of LVH by SMB.
基金The project supported by the Natural Science Foundation of Anhui Provincial(1308085QH145)
文摘OBJECTIVE To explore the underlying mechanisms involved in the effect of sesamin on aortic NO bioactivity in spontaneously hypertensive rat(SHR).METHODS Sesamin was orally administered for consecutive 8 weeks in SHR.Systolic blood pressure(SBP)was measured using the tail-cuff method.The aortas were isolated and in vitro vascular reactivity studies were performed.Superoxide anion production in carotid arteries was assessed by dihydroethidium fluorescence staining.The protein expression of endothelial nitric oxide synthase(eNOS),phosphorylated eNOS(P-eNOS),dihydrofolate reductase(DHFR),nicotinamide adenine dinucleotide phosphate(NADPH)oxidase subunit p47 phox and copper,zinc-superoxide dismutase(Cu/Zn-SOD)in aortas was detected by Western blotting.The dimeric form of eNOS in aortas was determined by low-temperature SDS-PAGE.Aortic level of nitrotyrosine and activities of antioxidant enzymes,namely,total SOD(T-SOD),glutathione peroxidase(GPx)and catalase were also detected.RESULTS In SHR,sesamin treatment reduced SBP,improved vascular relaxation induced by acetylcholine and enhanced aortic NO bioactivity.Sesamin treatment enhanced NO biosynthesis in SHR aortas was due to upregulated P-eNOS and suppressed eNOS uncoupling,and the latter effect might be attributed to decreased nitrotyrosine and upregulated DHFR.Sesamin also reducd the NO oxidative inactivation and decreased the superoxide anion production through downregulation of p47 phox and amelioration of eNOS uncoupling.In addition,sesamin treatment did not alter the levels of GPx and catalase activity but obviously reduced the compensatory elevated T-SOD activity and Cu/Zn-SOD protein expression.CONCLUSION Chronic treatment with sesamin could reduce hypertension and improve endothelial dysfunction through enhancement of NO bioactivity in SHRs aortas.
基金Supported by Grants from the National Center for Complementary and Alternative Medicine and the National Institutes ofHealth(NIH)Office of Dietary Supplements,No.5P50AT-00477the NIH Neuroscience Blueprint Mouse Phenotyping Coreat University of Alabama at Birmingham,No.P30 NS-057098the Faculty of Medicine,Khon Kaen University,Khon Kaen 40002,Thailand
文摘Taurine(2-aminoethanesulfonic acid) is a β-amino acid found in many tissues particularly brain, myocardium, and kidney. It plays several physiological roles including cardiac contraction, antioxidation, and blunting of hypertension. Though several lines of evidence indicate that dietary taurine can reduce hypertension in humans and in animal models, evidence that taurine supplementation reduces hypertension in humans has not been conclusive. One reason for the inconclusive nature of past studies may be that taurine having both positive and negative effects on cardiovascular system depending on when it is assessed, some effects may occur early, while others only appear later. Further, other consideration may play a role, e.g., taurine supplementation improves hypertension in spontaneously hypertensive rats on a low salt diet but fails to attenuate hypertension on a high salt diet. In humans, some epidemiologic studies indicate that people with high taurine and low salt diets display lower arterial pressure than those with low taurine and high salt diets. Differences in techniques for measuring arterial pressure, duration of treatment, and animal models likely affect the response in different studies. This review considers both the positive and negative effects of taurine on blood pressure in animal models and their applications for human interventions.
基金the General Financial Grant from the China Postdoctoral Science Foundation(No.2014M560722)the Natural Science Foundation of Sichuan University of Science and Engineering(No.2015RC30)the Science and Technology Support Program of Sichuan Province of China(No.2017RZ0083).
文摘The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis in hypertensive nephropathy are not fully understood.In the present study,we investigated the correlation of epithelium-like cells with glomerular injury,and the effects of early drug intervention with telmisartan,an anti-hypertensive drug,on the growth of epithelium-like cells.The results showed that the epithelium-like cells were obviously observed lining along the luminal surface of Bowman’s capsule in glomeruli,significantly resulting in the atrophy of the glomerular tuft.Some of the epithelium-like cells strongly expressed proliferating cell nuclear antigen(PCNA)and vimentin,indicating active cellular proliferation.The incidence of epithelium-like cells varied from 13.6%to 54.4%of glomeruli in 48-week-old SHRs,and from 5.1%to 18.0%of glomeruli in age-matched Wistar-Kyoto(WKY)rats(P<0.01).The linear regression analysis further confirmed an obvious correlation between the incidence of epithelium-like cells and the glomerular injury.Moreover,early intervention with telmisartan could dramatically attenuate the progression of epithelium-like cells growth.However,no significant effect of telmisartan on the established epithelium-like cells was observed.Taken together,we demonstrated the involvement of abnormal epithelium-like cells growth in glomerular injury during hypertensive nephropathy in SHRs,and firstly showed the positive effects of the anti-hypertensive drug on the progression of epithelium-like cells growth.
文摘Some citrus flavonoids have been reported to possess antioxidant activities that moderate endothelial dysfunction and show protective effects on cardiovascular disease. We have investigated the protective effects of nobiletin (5,6,7,8,3’,4’-hexamethoxy flavone) derived from the peel of Citrus depressa Hayata (Shiikuwasha), a citrus fruit produced in Okinawa prefecture in Japan on hypertension and thrombogenicity in cerebral vessels of stroke-prone spontaneously hypertensive rats (SHRSP). Nobiletin was added to the diet of male SHRSP (7 weeks old) for 4 weeks. The age-related increase in systolic blood pressure usually observed in SHRSP was significantly suppressed in the treated animals. Thrombogenesis in pial blood vessels, determined using a He-Ne laser technique, and antioxidant activity, assessed by measuring urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG), were significantly reduced after treatment. Urinary nitric oxide (NO) metabolites and acetylcholine-induced endothelial relaxation were increased after dietary intervention. These results strongly suggested that antihypertensive and antithrombotic effects of nobiletin may be related to an increase in bioavailable NO, possibly mediated by the scavenging of reactive oxygen species (ROS).
基金Supported by a grant from the National Natural Science Foundation of China(Grant No.81070219)
文摘Objective:To investigate the expression of phosphorylated peroxisome proliferators-activated receptor y(p-PPARY) in the aging thoracic aorta of spontaneously hypertensive rat(SHR) and the inhibitory effect of rosiglitazone on the phosphorylation of PPART.Methods:16,32 and 64 week-old Wistar-Kyoto rats(WKY) and SHR were randomly and respectively divided into WKY,SHR and SHR+rosiglitazone group(9 in each group).The rats in SHR+rosiglitazone group were treated with rosiglitazone(5 mg/kg,intragastrically) for 56 d,whereas normal saline was applied in WKY and SHR groups.Systolic blood pressure(SBP)of rats was measured by tail cuff method.Histopathological damage of thoracic aorta was analyzed using Hematoxylin-Eosin(HE) staining.Immunohistochemical staining and western blot were performed to test the level of p-PPARY protein in the thoracic aorta arising from each group.Results:The SBP in 16,32 and 64 week-old SHR were significantly higher as compared with those in matched WKY rats(P<0.05,respectively).HE staining showed increased content of smooth muscle cell,wrinkled lining endothelium and increased thickness of internal elastic lamina in the thoracic aorta of SHR.Immunohistochemical staining and western blot indicated that the levels of p-PPARY in the thoracic aorta arising from SHR were obviously higher than those in the thoracic aorta arising from WKY rats(P<0.05,respectively).Importantly,the high SBP,histopathological abnormalities of the thoracic aorta and elevated p-PPARY expression were prominently abrogated by rosiglitazone treatment in SHR(P<0.05,respectively).Furthermore,the SBP,histopathological abnormalities of the thoracic aorta and p-PPARY expression were positively correlated with age in SHR(P<0.05,respectively).Conclusions:The PPARY phosphorylation was observed in the thoracic aorta of SHR and its expression was increased by the increase of age.Furthermore,rosiglitazone inhibited the PPARY phosphorylation and suppressed vascular aging in SHR.
基金supported by Short Term Research Grant Scheme(304/PPSP/6131496)provided by Universiti Sains Malaysia.
文摘Objective:To investigate the effect of alpha-lipoic acid(ALA)supplementation on systolic blood pressure(SBP),renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats(SHR)and SHR administered with Nω-nitro-L-arginine methyl ester(L-NAME).Methods:Male rats were divided into four groups(SHR,SHR+ALA,SHR+L-NAME,SHR+ALA+L-NAME).The respective group of rats was administered with ALA(100 mg/kg/day)from age 4 weeks to 28 weeks and L-NAME(25 mg/kg/day)from age 16 weeks to 28 weeks.SBP was measured every two weeks and twenty four hour urine was collected at 4 weeks,16 weeks and 28 weeks for estimation of protein,creatinine and N-acetyl-e end of 28 weeks,rats were sacrificed and blood and kidneys colα-Dglucosaminidase.At thlected for assessment of blood creatinine,kidney thiobarbituric acid reactive substances,protein carbonyls,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,glutathione S-transferase,glutathione disulfide,glutathione,total antioxidant status and nitric oxide as well as histopathological examination.Results:ALA supplementation significantly reduced SBP of SHR and SHR+L-NAME rats when compared to their respective non-supplemented groups.Renal oxidant status markers including thiobarbituric acid reactive substances and protein carbonyls were significantly reduced on SHR and SHR+L-NAME rats supplemented with ALA at 28 weeks as well as ALA supplementation significantly increased renal antioxidants including superoxide dismutase,catalase,glutathione peroxidase,glutathione S-transferase,glutathione and glutathione/glutathione disulfide ratio at 28 weeks.No significant change in nitric oxide levels was observed between the ALA supplemented and non-supplemented groups.Renal dysfunction was ameliorated on ALA supplementation as evidenced by significant reduction in urine protein levels,N-acetyl-α-D-glucosaminidase activity and significant increase of creatinine clearance in SHR and SHR+L-NAME at 28 weeks.Renal histopathological examination showed that ALA supplementation prevented vascular damage in SHR and ameliorated glomerular damage in SHR+L-NAME at 28 weeks.Conclusions:ALA has hypotensive and renoprotective effects on both SHR and SHR+LNAME,which could be due to its ability to ameliorate oxidative stress in the kidneys.
文摘Aim To study the activity and mechanism of inhibition of myocardial hypertrophy of total flavonoids of Cydonia oblonga Mill. in spontaneously hypertensive rats. Methods Total flavonoids of COM （COMF） were sepa- rated and purified by the optimal process. SHtl were divided into 6 groups： SHR control group （SHR） , captopril group （SHR ＋ CAP, 25 μg · g^-1）, Eucommia ulmoides Oliver group （SHR ＋ EUO, 30 μg · g^-1）, low （SHR ＋ COMF-L, 40 μg · g^-1） ,middle （SHR ＋ COMF-M, 80 μg· g^-1） and high dose （SHR ＋ COMF-H, 160 μg · g^-1） of COMF groups. Wistar-Kyoto （WKY） rats （n= 8 ） were given distilled water as control The drugs were given by intragastric administration for 16 weeks. The histological and pathological examination of the heart were performed and organic damage were valued. The levels of Ang II and ALD in blood and heart were evaluated. The mRNA and protein expression of ACE, ACE2 and AT~ was determined by RT-PCR and Western blot to evaluate the effect of COMF on RAAS. Results Compared with SHR control group, HW, HW/BW, LVM and LVM/BW de- creased in SHR ＋ COMF-M and SHR ＋ COMF-H groups; Cadiomyocyte hypertrophy was inhibited in COMF groups; The concentration of Ang 11 and ALD in heart and blood decreased; ACE and AT1 mRNA and protein ex- pression in heart tissue decreased while ACE2 mRNA expression increased （P 〈 0.01 or P 〈 0.05） , Conclusion Total flavonoids of Cydonia oblonga Mill. showed the effect of inhibition of myocardial hypertrophy in spontaneously hypertensive rats and the mechanism was related to. inhibit the activity of Renin-angiotensin-aldosterone system.
基金the National Natural Science Foundation of China (81370361)Science and Technology Commission of Shanghai Municipality (12140902800)Scientific and Technical Project of Shanghai Chest Hospital (2014YZDH20300).
文摘Objective To explore the effectiveness of renal denervation (RDN) on blood pressure with the appropriate dosage of phenol/ethanol solution in spontaneously hypertensive rats (SHRs). Methods RDN was performed on the bilateral renal artery. Forty SHRs were divided into four groups according on the dosage of phenol (10% phenol in absolute ethanol): sham group, 0.5 mL phenol group, 1 mL phenol group and 1.5 mL phenol group (n = 10 in each group). Blood pressure was measured by tail-cuff plethysmography. Plasma creatinine was determined four weeks after the treatment. The kidneys and renal arteries were collected and processed for histological examination. Results A sustained decrease in systolic blood pressure (SBP) was only observed after the application of 1 mL phenol for four weeks, while SBP was lowered during the first week after RDN and increased in the following three weeks in the 0.5 mL and 1.5 mL phenol groups compared with the sham group. Renal norepinephrine (NE) was significantly decreased four weeks after RDN in the 1 mL and 1.5 mL phenol group compared with the sham group, but not in the 0.5 ml group. RDN with 1 mL phenol obviously reduced glomerular fibrosis. Histopathological analysis showed that tyrosine hydroxylase immunoreactivity was lower in the 1 mL and 1.5 mL phenol groups compared with the sham group. Moderate renal artery damage occurred in the 1.5 mL phenol group. Conclusion Chemical denervation with 1 ml phenol (10% phenol in absolute ethanol) effectively and safely damaged peripheral renal sympathetic nerves and contributed to the sustained reduction of blood pressure in SHRs.
基金Supported by the Natural Science Foundation of China(No.81100695)the Japan Society for the Promotion of Science(JSPS)([C] 25462750)
文摘AIM: To investigate the alterations in both structure and contractile responsiveness of ocular ciliary artery(OCA) in spontaneously hypertensive rat(SHR).METHODS: In this experiment, 20-week-old male SHR and Wistar Kyoto rat(WKY) were studied. The heart rate(HR), the blood pressure(BP; the systolic BP and the diastolic BP) of rats with an electronic sphygmomanometer were measured. Vascular morphometry and isometric tension measurement were used to investigate the alterations in structure and contractility of OCA.RESULTS: A general narrowing of OCAs was observed in SHR compared to the control WYK. In SHR, the media of OCAs were thicker, the luminal diameters were smaller, and the media-to-lumen ratios were higher when compared with WKY(P<0.05). The contractions of OCAs evoked by norepinephrine were smaller in SHR compared to control(P<0.05). Then, OCAs were pretreated with iberiotoxin, L-NAME, or indomethacin 30 min before norepinephrineinduced contraction. Iberiotoxin(0.1 μmol/L) has not changed the norepinephrine-induced contractions in OCAs from both groups. However, L-NAME(100 μmol/L) increased the vasoconstrictions, the increased extents were similar in SHR and WKY(P>0.05). Indomethacin(10 μmol/L) decreased the contractions induced by norepinephrine in OCAs from WKY(P<0.05), but did not change those contractions in vessels from SHR(P>0.05).CONCLUSION: Our results demonstrate that the structure and function of OCAs are altered in hypertension. OCAs from SHR are remodeled with decreased lumen diameter and increased media-to-lumen ratio. Moreover, the contractile responsiveness of OCAs from SHR is diminished due to the disruption of vasoconstrictive effect of prostaglandins.
基金National Natural Science Foundation of China(81860732)Scientific and Technological Projects for Social Development in Guizhou Province of China([2011]3036)the State Key Laboratory of Cardiovascular Disease(2017kf-03)
文摘OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model group(SHR,receive distilled water)and SF treatment groups(SF 20,40 and 80 mg·kg^-1 per day,respectively).Age-matched male Wistar-Kyoto(WKY)rats gavaged with distilled water served as controls.After 12 weeks of treatment,the effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement,pathological analysis and the expression of atrial natriuretic peptide(ANP),myosin heavy chainβ(β-MHC)-a gene related to myocardial hypertrophy.In order to explore the mechanism of SF on myocardial hypertrophy,the calcium-sensing receptor(CaSR),calcineurin(CaN),nuclear factor of activated T cell 3(NFAT3),phosphorylation NFAT3(p-NFAT3),zinc finger transcription factor(GATA4),phosphorylation GATA4(p-GATA4),protein kinase Cβ(PKC-β),Raf-1,extracellular regulated protein kinase 1/2(ERK 1/2),phosphorylation ERK1/2(p-ERK 1/2)and mitogen-activated protein kinase phosphatase-1(MKP-1)were detected.RESULTS The myocardial hypertrophy parameters,myocardial cell cross section area,left ventricular wall thickness and expression of ANP and β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 were significantly increased,while the left ventricular cavity was significantly smaller,expression of p-NFAT3 and MKP-1 were significantly decreased,meanwhile,the ultra⁃structure of cardiomyocytes was significantly damaged in 26-week-old SHR rats.Notably,SF significantly ameliorated myocardial hyper⁃trophy in 26-week-old SHR rats;suppressed the overexpression of ANP,β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 and increased the expression of p-NFAT3 and MKP-1.CONCLUSION SF can inhibit cardiac hypertrophy in SHR rats,and the mechanism may be related to the inhibition of CaSR mediated signaling pathway.
文摘Objectives: 1) To reveal, among spontaneously hypertensive rats, subpopulations that diverge in attention to objects enriching an empty cross-maze;2) To evaluate effect of clinically efficient drug for treatment of attention deficiency atomoxetine on the attention to environmental cues in attentionally-low rats. Method: A novel paradigm that provides measure of attention towards enriching objects independent of general locomotor activity and spatial orientation is employed. The apparatus consists of 4-arm radial maze, two arms of which contain objects (enriched compartments). Animals exploring the objects typically stay longer in enriched parts of maze than in empty arms and have a higher score of enrichment discrimination ratio. Results: Frequency distribution of the enrichment discrimination ratio had clear bimodal shape that differed significantly from normal distribution suggesting the existence of subpopulations of attentionally-low and -high individuals. The attentionally-low phenotype did not show inferiority in spatial orientation as compared with attentionally-high phenotype. The phenotypes did not differ from each other in measures of locomo- tor activity and blood pressure. Atomoxetine (3 mg/kg, orally, once daily for 4 days) enhanced enrichment discrimina- tion in animals of attentionally-low phenotype. Single administration of the drug was ineffective. Conclusion: Popula- tion of spontaneously hypertensive rat includes two phenotypes of attentionally-low and -high individuals. Subchronic atomoxetine ameliorates attention to environmental cues in attentionally-low rats. The enrichment discrimination test could be useful in studies of neurobiology of attention deficit condition and for screening of novel drug candidates.
文摘Dietary γ-amino butyric acid (GABA) has been suggested to decrease systolic blood pressure. This study aimed to ex-amine the effects of dietary GABA on the life span of stroke-prone spontaneously hypertensive rats (SHRSPs). In this study, life span was determined for SHRSPs provided 1% NaCl solution or 0.01% GABA in 1% NaCl solution as drinking water. The life span of the GABA-fed group (76.3 ± 1.65 days) was significantly shorter than that of the control group (81.6 ± 0.88 days). The results of this study may not be applicable to humans. Future studies will be necessary to elucidate the mechanism underlying this phenomenon.
