Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induc...Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca^(2+)]_i, mitochondrial reactive oxygen species(mitoROS), and mitochondrial membrane potential of smooth muscle cells(A10 cells) were measured using laser scanning confocal microscopy. Triclosan treatment relaxed phenylephrine(PE)-and high K^(+)(KPSS)-induced constriction, and pre-treatment with triclosan inhibited PE-and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, triclosan also relaxed PE-and KPSS-induced constriction. Triclosan induces vasorelaxation without involving KATPchannel activation in smooth muscle cells of arteries.Triclosan treatment increased cytosolic [Ca^(2+)]_i, mitochondrial ROS production and depolarized mitochondrial membrane potential in A10 cells. In conclusion, triclosan induces mitochondrial uncoupling in vascular smooth muscle cells and relaxes the constricted rat mesenteric arteries and aorta of rats. The present results suggest that triclosan would indicate vasodilation effect if absorbed excessively in vivo.展开更多
Lannea microcrapa Engl. & K. Krause (Anacardiaceae) is a fruit and medicinal plant widely used in Burkina Faso. This plant is traditionally used in the treatment of hypertension. The aim of the present study was t...Lannea microcrapa Engl. & K. Krause (Anacardiaceae) is a fruit and medicinal plant widely used in Burkina Faso. This plant is traditionally used in the treatment of hypertension. The aim of the present study was to evaluate the vasorelaxant effects of the hydroethanolic extract from Lannea microcarpa trunk barks (HE_ELM) on the aorta isolated from NMRI mice. Phytochemical screening by HPTLC, assay of phenolic and flavonoid compounds, assessment of antioxidant activity (DPPH, ABTS, FRAP, and LPO), and myography of HE_ELM (1 - 2000 μg/mL) on mice thoracic aortas in the presence and absence of endothelium were carried out. Endothelium-dependent and endothelium-independant vasodilation were assessed by cumulative addition of Ach (1 nM - 10 μM) on aortic rings precontracted with the thromboxane analogue A2 agonist, 9,11-dideoxy9α,11α-methanoepoxy PGF2α (U46619). L-NAME was used to verify the involvement of NO production in the relaxation mechanism of the extract. Acute oral toxicity of HE_ELM was also evaluated. A phytochemical study revealed the presence of tannins, flavonoids, sterols and triterpenes, saponosides, and high levels of total phenolics and flavonoids. These compounds are thought to be responsible for the extract’s antioxidant and vasorelaxant properties. HE_ELM demonstrated significant antioxidant potential and induced aortic relaxation. Indeed, pharmacological parameters gave EC<sub>50</sub> values ranging from 596.45 ± 95.82 μg/mL to 749.48 ± 133.40 μg/mL and Emax values from 85.51% ± 9.59% to 96.81% ± 8.60% for the three conditions of vasodilation of the extract (p > 0.05). A complete antagonism of the contractile effect of U46619 was noted with 1 mg/mL HE_ELM. These results suggest that HE_ELM induces aortic relaxation through a concentration-dependent, endothelium-independent mechanism, possibly involving intracellular calcium mobilization of vascular cells. Acute oral toxicity tests of HE_ELM (2000 mg/kg) showed no mortality or adverse effects, suggesting the extract’s safety and potential as a therapeutic agent for hypertension. This discovery scientifically validates the use of the plant in alternative medicine to treat hypertension.展开更多
Objective:To evaluate antioxidant,anti-inflammatory,hepatoprotective and vasorelaxant activities of Pupulus nigra flower buds ethanolic extract.Methods:Antioxidant and anti-inflammatory activities of the extract were ...Objective:To evaluate antioxidant,anti-inflammatory,hepatoprotective and vasorelaxant activities of Pupulus nigra flower buds ethanolic extract.Methods:Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw edema.Protection from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver sections.Vasorelaxant effect was estimated in endothelium-intact and-nibbed rings of porcine coronary arteries precontracted with high concentration of U466I9.Results:The results showed a moderate antioxidant activity(40%),but potent anti-inflammatory activity(49.9%)on carrageenan-induced mice paw edema,and also as revealed by histopathologic examination,complete protection against AlCl_3-induced hepatic toxicity.Relaxant effects of the same exlracl on vascular preparation from porcine aorta precontracted with high concentration of U466I9 were considerable at 10^(-1)g/L,and comparable(P>0.05)between endothelium-intact(67.74%,IC_(50)0.04 mg/ml.)and-rubbed(72.72%,IC_(50)=0.075 mg/ml,)aortic rings.Conclusions:The extract exerted significant anti-inflammatory,hepatoprotective and vasorelaxant activities,the latter being cndothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties,probably related to an inhibition of Ca^(2+)influx.展开更多
Aim To evaluate the vasorelaxant effects of the flavonone pinocembrin in isolated rat basilar artery rings and to investigate its possible mechanisms. Methods The isotonic contractions of the basilar artery rings from...Aim To evaluate the vasorelaxant effects of the flavonone pinocembrin in isolated rat basilar artery rings and to investigate its possible mechanisms. Methods The isotonic contractions of the basilar artery rings from SD rats were recorded. Results Pinocembrin exerted vasorelaxation in a close-dependent manner in KCL （60 mmol · L^-1 ） or 5-HT （ 1 μmol · L^- 1）-induced sustained contraction and partial loss of the vasorelaxation in endothelium- denuded rings. Pretreatment with pinocembrin （30 or 50 μmol · L^-1 ） attenuated contractile responses to KC1 （ 10 - 60 mmol · L^-1 ） and 5-HT （0. 001 - 10 μmol · L^-1 ）. The pinocembrin -induced vasorelaxation was significant- ly reduced by the nitric oxide synthase inhibitor Nco-nitro-L-arginine methyl ester （L-NAME, 100 μmol · L^-1） , the guanylate cyclase inhibitor ODQ （5 μmol · L^-1） and the cyclooxygenase inhibitor indomethacin （5 μmol · L^-l）. The voltage-dependent K＋ channel blocker 4-aminopyridine （100 μmol · L^-1）, the ATP-sensitive K ＋ channel blocker glibenclamide （10μmol · L^-1） and Ca2＋-activated K ＋ channel blocker tetraethylammonium （1 retool· L^-1） remarkably attenuated pinocembrin-induced relaxations. Pinocembrin also inhibited contraction in- duced by increasing external calcium in Ca2＋-free medium plus 60 mmol · L^-1 KC1. Conclusion These results demonstrate that pinocembrin has a vasorelaxant effect on isolated rat basilar artery rings and may exert its action through an endothelium-dependent pathway, involving NO-cGMP, and also through an endothelium-independent 2＋ pathway, opening K ＋ channels and blockade of Ca channels.展开更多
Mortality from cardiovascular abnormalities is almost three times more prevalent in the diabetic population than that in the general population. Psidium guajave has been used traditionally for a long time as a medicin...Mortality from cardiovascular abnormalities is almost three times more prevalent in the diabetic population than that in the general population. Psidium guajave has been used traditionally for a long time as a medicinal herb to cure diabetes. Endothelial dependent vasorelaxation effect of Psidium guajave extract on normal aortic rings was observed. This study was designed to investigate the endothelium and nitric oxide roles inPGE-induced vasorelaxation in diabetic rat vessel. Diabetes was induced by a single intraperitoneal injection of streptozotocin. Eight weeks later, superior mesenteric arteries of non-diabetic and diabetic groups were isolated and perfused according to the McGregor method. Prepared vascular beds were constricted with phenylephrine to induce 70% - 75% of maximal constriction. Psidium guajave extract at concentrations of 0.1 to 4 mg/100ml added to the medium and perfusion pressure was recorded. Baseline perfusion pressure of diabetic group was significantly higher than non-diabetic rats in both intact and denuded endothelium. Psidium guajave extract caused a significantly dose depended decrease in perfusion pressure in non-diabetic and diabetic groups in both intact and denuded endothelium. In the presence of N (ω)-nitro-L-arginine methyl ester, Psidium guajave ex-tractinduced relaxation in intact mesenteric beds of non-diabetic and diabetic animals was not suppressed. From the results of this study, it may be concluded that vasorelaxatory effect of Psidium guajave extract is not mediated by endothelium and nitric oxide in both diabetic and non-diabetic vessel and supports the use of the plant’s leaves as a natural, adjunct phytomedicine in the management of diabetes vessel complications.展开更多
Objective:To investigate the vasorelaxant effect of organic extracts from Apium graveolens(A.graveolens)which is a part of a group of plants subjected to pharmacological and phytochemical study with the purpose of off...Objective:To investigate the vasorelaxant effect of organic extracts from Apium graveolens(A.graveolens)which is a part of a group of plants subjected to pharmacological and phytochemical study with the purpose of offering it as an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects.Methods:An ex vivo method was employed to assess the vasorelaxant activity.This consisted of using rat aortic rings with and without endothelium precontracted with norepinephrine.Results:All extracts caused concentration-dependent relaxation in precontracted aortic rings with and without endothelium;the most active extracts were Dichloromethane and Ethyl Acetate extracts from A.graveolens.These results suggested that secondary metabolites responsible for the vasorelaxant activity belong to a group of compounds of medium polarity.Also,our evidence showed that effect induced by dichloromethane and ethyl acetate extracts from A.graveolens is mediated probably by calcium antagonism.Conclusions:A.graveolens represents an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects.展开更多
Objective: To explore the antihypertensive effect of extracts from the leaves of Hedera helix(H. helix) on normotensive and hypertensive rats in-vivo followed by vasodilatory studies in-vitro.Methods: The crude methan...Objective: To explore the antihypertensive effect of extracts from the leaves of Hedera helix(H. helix) on normotensive and hypertensive rats in-vivo followed by vasodilatory studies in-vitro.Methods: The crude methanolic extract was prepared and the activity directed fractionation was carried out. Spectrophotometric analysis of total phenolic and flavonoid content was also done. HPLC analysis was performed for the detection of hederacoside C. In-vivo blood pressure study was carried out in normotensive and high salt-induced hypertensive SpragueDawley rats. Isolated aortic tissues from rat and rabbit were used for in-vitro studies. The effects were recorded and analyzed through PowerL ab data acquisition system. Results: Crude extract of H. helix(1-30 mg/kg) decreased blood pressure to greater extent in high salt-induced hypertensive rats in-vivo compared to the normotensive [Max. fall(58.59±0.02) mm Hg vs.(67.53±3.07) mmH g]. The n-hexane, chloroform, ethyl acetate and aqueous fractions were also checked. These fractions were more effective in hypertensive rats. Aqueous fraction was more potent and n-hexane the least. In isolated rat aortic rings precontracted with phenylephrine, crude extract induced endothelium-dependent effect. The endothelium-dependent component of vasodilatory effect was ablated with L-NAME, and denudation of endothelium. The aqueous fraction was most potent vasodilator. In aortic rings from hypertensive rats, extract and fractions produced partial endothelium-independent effect which was not affected by pretreatment with L-NAME, indicating endothelium dysfunction in the hypertensive rats and suggesting additional vasodilatory mechanisms. In rabbit aorta, the extract and fractions also inhibited phenylephrine and high K^+-induced precontractions, and shifted Ca^(++) concentration–response curves. Conclusions: Our findings indicate that extract and fractions of H. helix are antihypertensive remedies, which is the outcome of vasodilatory effect. This vasodilatory effect is mediated through nitric oxide and Ca^(++) antagonism.展开更多
Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth m...Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine(PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K^+(KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PEbut not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE-and KPSSinduced aorta constriction. Transmission electron microscopy(TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells,and verapamil prevented both PE-and KPSS-induced excessive mitochondrial fission in aortic smoothmuscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells(A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.展开更多
Objective: To evaluate vasorelaxant and vasoconstriction effects of Zingiber officinale var. rubrum(ZOVR)on live rats and isolated aortic rings of spontaneously hypertensive rats(SHRs).Methods: Extracts of ZOVR were s...Objective: To evaluate vasorelaxant and vasoconstriction effects of Zingiber officinale var. rubrum(ZOVR)on live rats and isolated aortic rings of spontaneously hypertensive rats(SHRs).Methods: Extracts of ZOVR were subjected to in-vivo antihypertensive screening using noninvasive blood pressures in SHRs. The most potent extract, ZOVR petroleum ether extract(ZOP) was then fractionated using n-hexane, chloroform and water. Isolated thoracic aortic rings were harvested and subjected to vascular relaxation studies of n-hexane fraction of ZOP(HFZOP) with incubation of different antagonists such as Nω-nitro-L-arginine methyl ester(L-NAME, 10 μmol/L), indomethacin(10 μmol/L), methylene blue(10 μmol/L), atropine(1 μmol/L), glibenclamide(10 μmol/L), prazosin(0.01 μmol/L), and propranolol(1 μmol/L).Results: During the screening of various ZOVR extracts, ZOP produced the most reduction in blood pressures of SHRs and so did HFZOP. HFZOP significantly decreased phenylephrine-induced contraction and enhanced acetylcholine-induced relaxation. L-NAME, indomethacin, methylene blue, atropine, and glibenclamide significantly potentiated the vasorelaxant effects of HFZOP. Propranolol and prazosin did not alter the vasorelaxant effects of HFZOP. HFZOP significantly suppressed the Ca2+-dependent contraction and influenced the ratio of the responses to phenylephrine in Ca2+-free medium.Conclusion: This study demonstrates that ZOP may exert an antihypertensive effect in the SHR model. Its possible vascular relaxation mechanisms involve nitric oxide and prostacyclin release, activation of cGMP-KATP channels, stimulation of muscarinic receptors, and transmembrane calcium channel or Ca2+release from intracellular stores. Possible active compounds that contribute to the vasorelaxant effects are 6-gingerol, 8-gingerol and 6-shogaol.展开更多
OBJECTIVE: To investigate the effect of osthole on isolated thoracic aortic rings, and to determine the potential mechanism of action.METHODS: Thoracic aortas were isolated from Wistar rats, and were suspended in tiss...OBJECTIVE: To investigate the effect of osthole on isolated thoracic aortic rings, and to determine the potential mechanism of action.METHODS: Thoracic aortas were isolated from Wistar rats, and were suspended in tissue organ chambers for vascular tension measurement. The effect of cumulative osthole(10-9, 10-8, 10-7, 10-6, and 10-5 mol/L) on endothelium-intact and endothelium-denuded thoracic aortic rings pre-contracted with phenylephrine(PE, 10-6 mol/L) or KCl(6 × 10-2 mol/L) was recorded. Histomorphological changes of thoracic aorta were analyzed by hematoxylin-eosin. The effects of different osthole concentrations on endothelium-intact aortic rings, which were pre-inhibited with the non-selective nitric oxide synthase inhibitor L-Arg(NO2)-OMe·HCl(3 × 10-4 mol/L), endothelium-derived nitric oxide synthase inhibitor Nω-nitro-L-arginine(3 × 10-4 mol/L), guanylate cyclase inhibitor 1 H-[1,2,4] oxadiazolo [4,3-α]quinoxaline-1-one(10-5 mol/L), cyclooxygenase inhibitor indometacin(10-5 mol/L), and the Ca2+-activated potassium channel inhibitor tetraethylammonium nitrate(10-5 mol/L), and then contracted with PE, were examined. Aortic rings incubated with osthole(10-5 mol/L), phentolamine(10-5 mol/L), or verapamil(10-5 mol/L) in Ca2+-free Krebs-Henseleit solution(KHS) were stimulated with PE or KCl.RESULTS: There was a dose-dependent increase in vasorelaxation of isolated thoracic aortic rings(both with and without endothelium) with increasing osthole concentration. Hematoxylin-eosin staining showed that osthole significantly improved thoracic aorta ring morphology. Compared with the control group, there were also significant differences after incubation with L-Arg(NO2)-OMe ω-nitro-L-arginine, and 1 H-[1,2,4] oxadiazo·lo HCl,N [4,3-α] quinoxaline-1-one(P < 0.05 for all). The relaxation rate of the rings in the osthole group incubated with indometacin and tetraethylammonium nitrate were similar to controls. In Ca2+-free KHS, the PE-induced contraction was similar between the osthole(4.37% ± 0.41%) and control(4.21% ± 1.33%)groups. However, after cumulative CaCl2(0.5, 1, 1.5,2, 2.5, and 3 mmol/L), the Ca2+-induced contraction was significantly inhibited in the osthole and phentolamine groups compared with controls(P < 0.05).After cumulative CaCl2 was added to Ca2+-free KHS(high K+ concentration), the contraction rate was significantly higher than both of the control and the osthole groups(P < 0.05). The contraction rate in the osthole group was higher than the verapamil group(P < 0.05).CONCLUSION: Osthole has a vasorelaxant effect on isolated rat thoracic aortic rings, via inhibition of both receptor-operated and voltage-dependent Ca2+channels in arterial smooth muscle, leading to decreased Ca2+ influx, and via inhibition of nitric oxide release on arterial endothelial cells.展开更多
Objective: This study aims to evaluate the vasodilatory effect of Chenopodium ambrosioides on the isolated rat aorta, and to explore its mechanism of action.Methods: The vasorelaxant effect and the mode of action of v...Objective: This study aims to evaluate the vasodilatory effect of Chenopodium ambrosioides on the isolated rat aorta, and to explore its mechanism of action.Methods: The vasorelaxant effect and the mode of action of various extracts from the leaves of C. ambrosioides were evaluated on thoracic aortic rings isolated from Wistar rats. In addition, ethyl acetate and methanol fractions were analyzed, using thin-layer chromatography and high-performance liquid chromatography techniques, for their polyphenolic content.Results: The various active extracts of C. ambrosioides at four concentrations(10^(-3), 10^(-2), 10^(-1) and 1 mg/mL) relaxed the contraction elicited by phenylephrine, in a concentration-dependent manner.This effect seems to be endothelium-dependent, since the vasodilatory effect was entirely absent in denuded aortic rings. The vasorelaxant effect of the methanol fraction(MF) of C. ambrosioides at 1 mg/mL was also inhibited by atropine and tetraethylammonium. This effect remained unchanged by Nx-nitro-L-arginine methyl ester hydrochloride and glibenclamide. The preliminary phytochemical analysis showed that the leaves of C. ambrosioides are rich in phenolic and flavonoid derivatives.Conclusion: These results suggest that the MF of C. ambrosioides produces an endothelium-dependent relaxation of the isolated rat aorta, which is thought to be mediated mainly through stimulation of the muscarinic receptors, and probably involving the opening of Ca^(2+)-activated potassium channels.展开更多
Objective: It is well known that systemic insulin resistance (IR) is closely associated with the metabolic syndrome including type 2 diabetes and hypertension. However, it remains
Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by exte...Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism(ECD)calculation.Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.展开更多
Croton zambezicus Muell.Arg.(Euphorbiaceae)(Syn.C.amabilis Muell.Arg.,C.gratissimus Burch.)is a shrub or small tree reaching 10 m in height.The leaf decoction is used in Benin as anti-hypertensive,anti-microbial(urina...Croton zambezicus Muell.Arg.(Euphorbiaceae)(Syn.C.amabilis Muell.Arg.,C.gratissimus Burch.)is a shrub or small tree reaching 10 m in height.The leaf decoction is used in Benin as anti-hypertensive,anti-microbial(urinary infections)and to treat fever associated with malaria.We analysed the in vitro and in vivo vasorelaxant activity展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81373406 and 81421063)
文摘Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca^(2+)]_i, mitochondrial reactive oxygen species(mitoROS), and mitochondrial membrane potential of smooth muscle cells(A10 cells) were measured using laser scanning confocal microscopy. Triclosan treatment relaxed phenylephrine(PE)-and high K^(+)(KPSS)-induced constriction, and pre-treatment with triclosan inhibited PE-and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, triclosan also relaxed PE-and KPSS-induced constriction. Triclosan induces vasorelaxation without involving KATPchannel activation in smooth muscle cells of arteries.Triclosan treatment increased cytosolic [Ca^(2+)]_i, mitochondrial ROS production and depolarized mitochondrial membrane potential in A10 cells. In conclusion, triclosan induces mitochondrial uncoupling in vascular smooth muscle cells and relaxes the constricted rat mesenteric arteries and aorta of rats. The present results suggest that triclosan would indicate vasodilation effect if absorbed excessively in vivo.
文摘Lannea microcrapa Engl. & K. Krause (Anacardiaceae) is a fruit and medicinal plant widely used in Burkina Faso. This plant is traditionally used in the treatment of hypertension. The aim of the present study was to evaluate the vasorelaxant effects of the hydroethanolic extract from Lannea microcarpa trunk barks (HE_ELM) on the aorta isolated from NMRI mice. Phytochemical screening by HPTLC, assay of phenolic and flavonoid compounds, assessment of antioxidant activity (DPPH, ABTS, FRAP, and LPO), and myography of HE_ELM (1 - 2000 μg/mL) on mice thoracic aortas in the presence and absence of endothelium were carried out. Endothelium-dependent and endothelium-independant vasodilation were assessed by cumulative addition of Ach (1 nM - 10 μM) on aortic rings precontracted with the thromboxane analogue A2 agonist, 9,11-dideoxy9α,11α-methanoepoxy PGF2α (U46619). L-NAME was used to verify the involvement of NO production in the relaxation mechanism of the extract. Acute oral toxicity of HE_ELM was also evaluated. A phytochemical study revealed the presence of tannins, flavonoids, sterols and triterpenes, saponosides, and high levels of total phenolics and flavonoids. These compounds are thought to be responsible for the extract’s antioxidant and vasorelaxant properties. HE_ELM demonstrated significant antioxidant potential and induced aortic relaxation. Indeed, pharmacological parameters gave EC<sub>50</sub> values ranging from 596.45 ± 95.82 μg/mL to 749.48 ± 133.40 μg/mL and Emax values from 85.51% ± 9.59% to 96.81% ± 8.60% for the three conditions of vasodilation of the extract (p > 0.05). A complete antagonism of the contractile effect of U46619 was noted with 1 mg/mL HE_ELM. These results suggest that HE_ELM induces aortic relaxation through a concentration-dependent, endothelium-independent mechanism, possibly involving intracellular calcium mobilization of vascular cells. Acute oral toxicity tests of HE_ELM (2000 mg/kg) showed no mortality or adverse effects, suggesting the extract’s safety and potential as a therapeutic agent for hypertension. This discovery scientifically validates the use of the plant in alternative medicine to treat hypertension.
基金Supported by Ministry of Higher Education and Scientific Research of Algeria(CNEPRU Grant No.F00620100006)
文摘Objective:To evaluate antioxidant,anti-inflammatory,hepatoprotective and vasorelaxant activities of Pupulus nigra flower buds ethanolic extract.Methods:Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw edema.Protection from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver sections.Vasorelaxant effect was estimated in endothelium-intact and-nibbed rings of porcine coronary arteries precontracted with high concentration of U466I9.Results:The results showed a moderate antioxidant activity(40%),but potent anti-inflammatory activity(49.9%)on carrageenan-induced mice paw edema,and also as revealed by histopathologic examination,complete protection against AlCl_3-induced hepatic toxicity.Relaxant effects of the same exlracl on vascular preparation from porcine aorta precontracted with high concentration of U466I9 were considerable at 10^(-1)g/L,and comparable(P>0.05)between endothelium-intact(67.74%,IC_(50)0.04 mg/ml.)and-rubbed(72.72%,IC_(50)=0.075 mg/ml,)aortic rings.Conclusions:The extract exerted significant anti-inflammatory,hepatoprotective and vasorelaxant activities,the latter being cndothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties,probably related to an inhibition of Ca^(2+)influx.
文摘Aim To evaluate the vasorelaxant effects of the flavonone pinocembrin in isolated rat basilar artery rings and to investigate its possible mechanisms. Methods The isotonic contractions of the basilar artery rings from SD rats were recorded. Results Pinocembrin exerted vasorelaxation in a close-dependent manner in KCL （60 mmol · L^-1 ） or 5-HT （ 1 μmol · L^- 1）-induced sustained contraction and partial loss of the vasorelaxation in endothelium- denuded rings. Pretreatment with pinocembrin （30 or 50 μmol · L^-1 ） attenuated contractile responses to KC1 （ 10 - 60 mmol · L^-1 ） and 5-HT （0. 001 - 10 μmol · L^-1 ）. The pinocembrin -induced vasorelaxation was significant- ly reduced by the nitric oxide synthase inhibitor Nco-nitro-L-arginine methyl ester （L-NAME, 100 μmol · L^-1） , the guanylate cyclase inhibitor ODQ （5 μmol · L^-1） and the cyclooxygenase inhibitor indomethacin （5 μmol · L^-l）. The voltage-dependent K＋ channel blocker 4-aminopyridine （100 μmol · L^-1）, the ATP-sensitive K ＋ channel blocker glibenclamide （10μmol · L^-1） and Ca2＋-activated K ＋ channel blocker tetraethylammonium （1 retool· L^-1） remarkably attenuated pinocembrin-induced relaxations. Pinocembrin also inhibited contraction in- duced by increasing external calcium in Ca2＋-free medium plus 60 mmol · L^-1 KC1. Conclusion These results demonstrate that pinocembrin has a vasorelaxant effect on isolated rat basilar artery rings and may exert its action through an endothelium-dependent pathway, involving NO-cGMP, and also through an endothelium-independent 2＋ pathway, opening K ＋ channels and blockade of Ca channels.
文摘Mortality from cardiovascular abnormalities is almost three times more prevalent in the diabetic population than that in the general population. Psidium guajave has been used traditionally for a long time as a medicinal herb to cure diabetes. Endothelial dependent vasorelaxation effect of Psidium guajave extract on normal aortic rings was observed. This study was designed to investigate the endothelium and nitric oxide roles inPGE-induced vasorelaxation in diabetic rat vessel. Diabetes was induced by a single intraperitoneal injection of streptozotocin. Eight weeks later, superior mesenteric arteries of non-diabetic and diabetic groups were isolated and perfused according to the McGregor method. Prepared vascular beds were constricted with phenylephrine to induce 70% - 75% of maximal constriction. Psidium guajave extract at concentrations of 0.1 to 4 mg/100ml added to the medium and perfusion pressure was recorded. Baseline perfusion pressure of diabetic group was significantly higher than non-diabetic rats in both intact and denuded endothelium. Psidium guajave extract caused a significantly dose depended decrease in perfusion pressure in non-diabetic and diabetic groups in both intact and denuded endothelium. In the presence of N (ω)-nitro-L-arginine methyl ester, Psidium guajave ex-tractinduced relaxation in intact mesenteric beds of non-diabetic and diabetic animals was not suppressed. From the results of this study, it may be concluded that vasorelaxatory effect of Psidium guajave extract is not mediated by endothelium and nitric oxide in both diabetic and non-diabetic vessel and supports the use of the plant’s leaves as a natural, adjunct phytomedicine in the management of diabetes vessel complications.
基金financed by grants from"Promotion of generation on innovative application of Knowledge and promotion of applied research or technological development"PROMEP-SEP 2012-2013,ofieio PROMEP/103.5/12/8308)"Programme for Strengthening Besearch"PROFI-IQROO 2012,and P/PIFI-2012-23MSI 0140/-09DCS
文摘Objective:To investigate the vasorelaxant effect of organic extracts from Apium graveolens(A.graveolens)which is a part of a group of plants subjected to pharmacological and phytochemical study with the purpose of offering it as an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects.Methods:An ex vivo method was employed to assess the vasorelaxant activity.This consisted of using rat aortic rings with and without endothelium precontracted with norepinephrine.Results:All extracts caused concentration-dependent relaxation in precontracted aortic rings with and without endothelium;the most active extracts were Dichloromethane and Ethyl Acetate extracts from A.graveolens.These results suggested that secondary metabolites responsible for the vasorelaxant activity belong to a group of compounds of medium polarity.Also,our evidence showed that effect induced by dichloromethane and ethyl acetate extracts from A.graveolens is mediated probably by calcium antagonism.Conclusions:A.graveolens represents an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects.
文摘Objective: To explore the antihypertensive effect of extracts from the leaves of Hedera helix(H. helix) on normotensive and hypertensive rats in-vivo followed by vasodilatory studies in-vitro.Methods: The crude methanolic extract was prepared and the activity directed fractionation was carried out. Spectrophotometric analysis of total phenolic and flavonoid content was also done. HPLC analysis was performed for the detection of hederacoside C. In-vivo blood pressure study was carried out in normotensive and high salt-induced hypertensive SpragueDawley rats. Isolated aortic tissues from rat and rabbit were used for in-vitro studies. The effects were recorded and analyzed through PowerL ab data acquisition system. Results: Crude extract of H. helix(1-30 mg/kg) decreased blood pressure to greater extent in high salt-induced hypertensive rats in-vivo compared to the normotensive [Max. fall(58.59±0.02) mm Hg vs.(67.53±3.07) mmH g]. The n-hexane, chloroform, ethyl acetate and aqueous fractions were also checked. These fractions were more effective in hypertensive rats. Aqueous fraction was more potent and n-hexane the least. In isolated rat aortic rings precontracted with phenylephrine, crude extract induced endothelium-dependent effect. The endothelium-dependent component of vasodilatory effect was ablated with L-NAME, and denudation of endothelium. The aqueous fraction was most potent vasodilator. In aortic rings from hypertensive rats, extract and fractions produced partial endothelium-independent effect which was not affected by pretreatment with L-NAME, indicating endothelium dysfunction in the hypertensive rats and suggesting additional vasodilatory mechanisms. In rabbit aorta, the extract and fractions also inhibited phenylephrine and high K^+-induced precontractions, and shifted Ca^(++) concentration–response curves. Conclusions: Our findings indicate that extract and fractions of H. helix are antihypertensive remedies, which is the outcome of vasodilatory effect. This vasodilatory effect is mediated through nitric oxide and Ca^(++) antagonism.
基金supported by the National Natural Science Foundation of China(Grant Nos.81373406 and 81421063)
文摘Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine(PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K^+(KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PEbut not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE-and KPSSinduced aorta constriction. Transmission electron microscopy(TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells,and verapamil prevented both PE-and KPSS-induced excessive mitochondrial fission in aortic smoothmuscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells(A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.
基金supported by the Fundamental Research Grant Scheme,Ministry of Higher Education,Malaysia(203/PFARMASI/6711408)MyPhD(MyBrain programme),Ministry of Higher Education,Malaysia.
文摘Objective: To evaluate vasorelaxant and vasoconstriction effects of Zingiber officinale var. rubrum(ZOVR)on live rats and isolated aortic rings of spontaneously hypertensive rats(SHRs).Methods: Extracts of ZOVR were subjected to in-vivo antihypertensive screening using noninvasive blood pressures in SHRs. The most potent extract, ZOVR petroleum ether extract(ZOP) was then fractionated using n-hexane, chloroform and water. Isolated thoracic aortic rings were harvested and subjected to vascular relaxation studies of n-hexane fraction of ZOP(HFZOP) with incubation of different antagonists such as Nω-nitro-L-arginine methyl ester(L-NAME, 10 μmol/L), indomethacin(10 μmol/L), methylene blue(10 μmol/L), atropine(1 μmol/L), glibenclamide(10 μmol/L), prazosin(0.01 μmol/L), and propranolol(1 μmol/L).Results: During the screening of various ZOVR extracts, ZOP produced the most reduction in blood pressures of SHRs and so did HFZOP. HFZOP significantly decreased phenylephrine-induced contraction and enhanced acetylcholine-induced relaxation. L-NAME, indomethacin, methylene blue, atropine, and glibenclamide significantly potentiated the vasorelaxant effects of HFZOP. Propranolol and prazosin did not alter the vasorelaxant effects of HFZOP. HFZOP significantly suppressed the Ca2+-dependent contraction and influenced the ratio of the responses to phenylephrine in Ca2+-free medium.Conclusion: This study demonstrates that ZOP may exert an antihypertensive effect in the SHR model. Its possible vascular relaxation mechanisms involve nitric oxide and prostacyclin release, activation of cGMP-KATP channels, stimulation of muscarinic receptors, and transmembrane calcium channel or Ca2+release from intracellular stores. Possible active compounds that contribute to the vasorelaxant effects are 6-gingerol, 8-gingerol and 6-shogaol.
基金Supported by National Natural Science Foundation of China(Study on the association between the composition of pungent traditional Chinese medicine and the effect of promoting blood circulation,No.81273901)
文摘OBJECTIVE: To investigate the effect of osthole on isolated thoracic aortic rings, and to determine the potential mechanism of action.METHODS: Thoracic aortas were isolated from Wistar rats, and were suspended in tissue organ chambers for vascular tension measurement. The effect of cumulative osthole(10-9, 10-8, 10-7, 10-6, and 10-5 mol/L) on endothelium-intact and endothelium-denuded thoracic aortic rings pre-contracted with phenylephrine(PE, 10-6 mol/L) or KCl(6 × 10-2 mol/L) was recorded. Histomorphological changes of thoracic aorta were analyzed by hematoxylin-eosin. The effects of different osthole concentrations on endothelium-intact aortic rings, which were pre-inhibited with the non-selective nitric oxide synthase inhibitor L-Arg(NO2)-OMe·HCl(3 × 10-4 mol/L), endothelium-derived nitric oxide synthase inhibitor Nω-nitro-L-arginine(3 × 10-4 mol/L), guanylate cyclase inhibitor 1 H-[1,2,4] oxadiazolo [4,3-α]quinoxaline-1-one(10-5 mol/L), cyclooxygenase inhibitor indometacin(10-5 mol/L), and the Ca2+-activated potassium channel inhibitor tetraethylammonium nitrate(10-5 mol/L), and then contracted with PE, were examined. Aortic rings incubated with osthole(10-5 mol/L), phentolamine(10-5 mol/L), or verapamil(10-5 mol/L) in Ca2+-free Krebs-Henseleit solution(KHS) were stimulated with PE or KCl.RESULTS: There was a dose-dependent increase in vasorelaxation of isolated thoracic aortic rings(both with and without endothelium) with increasing osthole concentration. Hematoxylin-eosin staining showed that osthole significantly improved thoracic aorta ring morphology. Compared with the control group, there were also significant differences after incubation with L-Arg(NO2)-OMe ω-nitro-L-arginine, and 1 H-[1,2,4] oxadiazo·lo HCl,N [4,3-α] quinoxaline-1-one(P < 0.05 for all). The relaxation rate of the rings in the osthole group incubated with indometacin and tetraethylammonium nitrate were similar to controls. In Ca2+-free KHS, the PE-induced contraction was similar between the osthole(4.37% ± 0.41%) and control(4.21% ± 1.33%)groups. However, after cumulative CaCl2(0.5, 1, 1.5,2, 2.5, and 3 mmol/L), the Ca2+-induced contraction was significantly inhibited in the osthole and phentolamine groups compared with controls(P < 0.05).After cumulative CaCl2 was added to Ca2+-free KHS(high K+ concentration), the contraction rate was significantly higher than both of the control and the osthole groups(P < 0.05). The contraction rate in the osthole group was higher than the verapamil group(P < 0.05).CONCLUSION: Osthole has a vasorelaxant effect on isolated rat thoracic aortic rings, via inhibition of both receptor-operated and voltage-dependent Ca2+channels in arterial smooth muscle, leading to decreased Ca2+ influx, and via inhibition of nitric oxide release on arterial endothelial cells.
基金sponsored by funding from CNRST, Morocco (Project URAC-40)from Belgium (Program 3, CUD Project)
文摘Objective: This study aims to evaluate the vasodilatory effect of Chenopodium ambrosioides on the isolated rat aorta, and to explore its mechanism of action.Methods: The vasorelaxant effect and the mode of action of various extracts from the leaves of C. ambrosioides were evaluated on thoracic aortic rings isolated from Wistar rats. In addition, ethyl acetate and methanol fractions were analyzed, using thin-layer chromatography and high-performance liquid chromatography techniques, for their polyphenolic content.Results: The various active extracts of C. ambrosioides at four concentrations(10^(-3), 10^(-2), 10^(-1) and 1 mg/mL) relaxed the contraction elicited by phenylephrine, in a concentration-dependent manner.This effect seems to be endothelium-dependent, since the vasodilatory effect was entirely absent in denuded aortic rings. The vasorelaxant effect of the methanol fraction(MF) of C. ambrosioides at 1 mg/mL was also inhibited by atropine and tetraethylammonium. This effect remained unchanged by Nx-nitro-L-arginine methyl ester hydrochloride and glibenclamide. The preliminary phytochemical analysis showed that the leaves of C. ambrosioides are rich in phenolic and flavonoid derivatives.Conclusion: These results suggest that the MF of C. ambrosioides produces an endothelium-dependent relaxation of the isolated rat aorta, which is thought to be mediated mainly through stimulation of the muscarinic receptors, and probably involving the opening of Ca^(2+)-activated potassium channels.
文摘Objective: It is well known that systemic insulin resistance (IR) is closely associated with the metabolic syndrome including type 2 diabetes and hypertension. However, it remains
基金supported by the National Key R&D Program of China(No.2017YFC1703802)the National Natural Science Foundation of China(Nos.U1801287,81630095,and 81803398)+1 种基金the Science and Technology Planning Project of Guangdong Province(No.2018B020207008)the High-performance Super Computing Platform of Jinan University
文摘Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism(ECD)calculation.Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.
文摘Croton zambezicus Muell.Arg.(Euphorbiaceae)(Syn.C.amabilis Muell.Arg.,C.gratissimus Burch.)is a shrub or small tree reaching 10 m in height.The leaf decoction is used in Benin as anti-hypertensive,anti-microbial(urinary infections)and to treat fever associated with malaria.We analysed the in vitro and in vivo vasorelaxant activity
