The aim of the current study was to investigate the pharmacological activity of glabridinon the isolated human saphenous vein (SV) and explore the underlying mechanisms. Samples of patients' SVs were removed durin...The aim of the current study was to investigate the pharmacological activity of glabridinon the isolated human saphenous vein (SV) and explore the underlying mechanisms. Samples of patients' SVs were removed during bypass surgery, and 4-mm lengths of the vessels were placedin Krebs solution at ±4℃ and hung in an isolated organ bath to assess their contraction/relaxationresponses. The contraction/relaxation responses were recorded to observe if the cyclic guanosinemonophosphate (cGMP)/protein kinase G (PKG) pathway mediates the relaxant effect of glabridinafter treatment with blockers like ODQ (a guanylate cyclase inhibitor), KT5823 (a PKG inhibitor),isobutylmethylxanthine [IBMX, a phosphodiesterase (PDE) inhibitor], and cantharidin [Cant,a myosin light-chain phosphatase (MLCP) inhibitor]. Moreover, nitric oxide (NO), cGMP, andPKG levels in SV tissues were determined by ELISA after incubation with glabridin, N(o)-nitro-L-arginine methyl ester (L-Name, a NO synthetase inhibitor), phenylephrine (PE), ODQ, IBMX,and KT5823. The results showed that glabridin relaxed the vascular smooth muscle of humanSV pretreated with PE in a dose-dependent manner, which was independent of the endothelium.The vasorelaxant effect of glabridin was only inhibited by iberiotoxin (IbTX), Cant, and KT5823.Glabridin increased cGMP and PKG levels in SV homogenates, whereas it did not alter the NOlevel. The enhancing efects of cGMP and PKG levels by glabridin were abolished by ODQ andKT5823. In conclusion, glabridin has a vasorelaxant effect, which is associated with the activationof BKc. channels and inhibition of PDE.展开更多
Aim This study sought to investigate the effect of chronic nicotine exposure on vascular function and to identify the underlying mechanisms. Methods Isolated organ bath studies were performed to examine the effects of...Aim This study sought to investigate the effect of chronic nicotine exposure on vascular function and to identify the underlying mechanisms. Methods Isolated organ bath studies were performed to examine the effects of chronic nicotine exposure on vascular reactivity of the aorta in Sprague-Dawley rats. We used various analogues and blockers of the cGMP-dependent protein kinase （PKG） pathway as well as molecular techniques to identify the un- derlying mechanisms. Results Chronic nicotine exposure reduced periaortic fat and specifically enhanced smooth muscle relaxation, although aortic adventitial fat and endothelium function were not affected. The soluble guanylyl cyclase inhibitor ODQ or PKG inhibitor Rp-8-Br-PET-cGMP abolished the difference in relaxation between the sa- line and nicotine group, and the cGMP analogue 8-Br-cGMP mimicked the difference in relaxation. PKG protein expression and activity were not altered after nicotine treatment. Conclusion Chronic nicotine exposure enhances vascular smooth muscle relaxation through a cGMP-dependent PKG pathway. Our findings provide novel insights in- to nicotine pharmacology.展开更多
Background:High salt-diets have become significant threats to human health,resulting in hypertension and cardiovascular diseases.Hypertensive disorders during pregnancy are complicated,since the maternal cardiovascula...Background:High salt-diets have become significant threats to human health,resulting in hypertension and cardiovascular diseases.Hypertensive disorders during pregnancy are complicated,since the maternal cardiovascular system undergoes extensive physiological changes during pregnancy.High-salt diets during pregnancy can disturb the intrauterine environment and negatively affect fetal development.Therefore,we explored how high-salt diets during pregnancy could affect the offspring.Methods:Rats were divided into three groups and fed with low,normal,and high salt diets.The offspring were separated into three groups after weaning based on dietary salt concentration.The blood pressure and urine protein content of both dams and offspring were measured.To evaluate cardiac function,we used Masson staining and immunodetection to confirm the fibrosis status.Finally,we extracted protein from cardiac tissue to test the expression levels of the Nitric Oxide(NO)/cGMP-dependent protein kinase I(PKGI)pathway and the angiotensin receptor.Results:High-salt diets increased blood pressure,and offspring previously exposed to high-salt environments were predisposed to hypertension.High-salt diets were also found to induce cardiac fibrosis and exacerbate fibrosis in offspring and alter the epithelial-mesenchymal transition(EMT).Under these conditions,the NO/PKGI pathway was activated in cardiac tissue and the type-1angiotensin II receptor(AT1R)was upregulated,though the type-2 angiotensin II receptor(AT2R)had the opposite effect.Conclusion:High-salt diets induce high blood pressure and increase predisposition to hypertension in offspring.They are accompanied by cardiac fibrosis,which could be caused by the activation of NO/PKGI and upregulation of AT1R.展开更多
文摘The aim of the current study was to investigate the pharmacological activity of glabridinon the isolated human saphenous vein (SV) and explore the underlying mechanisms. Samples of patients' SVs were removed during bypass surgery, and 4-mm lengths of the vessels were placedin Krebs solution at ±4℃ and hung in an isolated organ bath to assess their contraction/relaxationresponses. The contraction/relaxation responses were recorded to observe if the cyclic guanosinemonophosphate (cGMP)/protein kinase G (PKG) pathway mediates the relaxant effect of glabridinafter treatment with blockers like ODQ (a guanylate cyclase inhibitor), KT5823 (a PKG inhibitor),isobutylmethylxanthine [IBMX, a phosphodiesterase (PDE) inhibitor], and cantharidin [Cant,a myosin light-chain phosphatase (MLCP) inhibitor]. Moreover, nitric oxide (NO), cGMP, andPKG levels in SV tissues were determined by ELISA after incubation with glabridin, N(o)-nitro-L-arginine methyl ester (L-Name, a NO synthetase inhibitor), phenylephrine (PE), ODQ, IBMX,and KT5823. The results showed that glabridin relaxed the vascular smooth muscle of humanSV pretreated with PE in a dose-dependent manner, which was independent of the endothelium.The vasorelaxant effect of glabridin was only inhibited by iberiotoxin (IbTX), Cant, and KT5823.Glabridin increased cGMP and PKG levels in SV homogenates, whereas it did not alter the NOlevel. The enhancing efects of cGMP and PKG levels by glabridin were abolished by ODQ andKT5823. In conclusion, glabridin has a vasorelaxant effect, which is associated with the activationof BKc. channels and inhibition of PDE.
文摘Aim This study sought to investigate the effect of chronic nicotine exposure on vascular function and to identify the underlying mechanisms. Methods Isolated organ bath studies were performed to examine the effects of chronic nicotine exposure on vascular reactivity of the aorta in Sprague-Dawley rats. We used various analogues and blockers of the cGMP-dependent protein kinase （PKG） pathway as well as molecular techniques to identify the un- derlying mechanisms. Results Chronic nicotine exposure reduced periaortic fat and specifically enhanced smooth muscle relaxation, although aortic adventitial fat and endothelium function were not affected. The soluble guanylyl cyclase inhibitor ODQ or PKG inhibitor Rp-8-Br-PET-cGMP abolished the difference in relaxation between the sa- line and nicotine group, and the cGMP analogue 8-Br-cGMP mimicked the difference in relaxation. PKG protein expression and activity were not altered after nicotine treatment. Conclusion Chronic nicotine exposure enhances vascular smooth muscle relaxation through a cGMP-dependent PKG pathway. Our findings provide novel insights in- to nicotine pharmacology.
基金This work was supported by National Key R&D Program of China(No.2018YFC1002902)the National Natural Science Foundation(No.81830045,81671533 and 81571518)General program of Guangdong province Natural Science Foundation(No.2020A1515010273).
文摘Background:High salt-diets have become significant threats to human health,resulting in hypertension and cardiovascular diseases.Hypertensive disorders during pregnancy are complicated,since the maternal cardiovascular system undergoes extensive physiological changes during pregnancy.High-salt diets during pregnancy can disturb the intrauterine environment and negatively affect fetal development.Therefore,we explored how high-salt diets during pregnancy could affect the offspring.Methods:Rats were divided into three groups and fed with low,normal,and high salt diets.The offspring were separated into three groups after weaning based on dietary salt concentration.The blood pressure and urine protein content of both dams and offspring were measured.To evaluate cardiac function,we used Masson staining and immunodetection to confirm the fibrosis status.Finally,we extracted protein from cardiac tissue to test the expression levels of the Nitric Oxide(NO)/cGMP-dependent protein kinase I(PKGI)pathway and the angiotensin receptor.Results:High-salt diets increased blood pressure,and offspring previously exposed to high-salt environments were predisposed to hypertension.High-salt diets were also found to induce cardiac fibrosis and exacerbate fibrosis in offspring and alter the epithelial-mesenchymal transition(EMT).Under these conditions,the NO/PKGI pathway was activated in cardiac tissue and the type-1angiotensin II receptor(AT1R)was upregulated,though the type-2 angiotensin II receptor(AT2R)had the opposite effect.Conclusion:High-salt diets induce high blood pressure and increase predisposition to hypertension in offspring.They are accompanied by cardiac fibrosis,which could be caused by the activation of NO/PKGI and upregulation of AT1R.
