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
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.
