Sesamin ameliorates arterial dysfunction in spontaneously hypertensive rats via downregulation of NADPH oxidase subunits and upregulation of eNOS expression
Abstract
Jun-xiu ZHANG, Jie-ren YANG*, Guo-xiang CHEN, Li-juan TANG, Wen-xing LI, Hui YANG, Xiang KONG
Department of Pharmacology, Third-Grade Pharmacology Laboratory of State Administration of Traditional Chinese Medicine, Wannan Medical College, Wuhu 241001, China
Aim: Sesamin is one of the major lignans in sesame seeds with antihyperlipidemic, antioxidative and antihypertensive activities. The aim of this study was to examine the effects of sesamin on arterial function in spontaneously hypertensive rats (SHRs).
Methods: SHRs were orally administered sesamin (40, 80 and 160 mg·kg-1·d-1) for 16 weeks. After the rats were killed, thoracic aortas were dissected out. The vasorelaxation responses of aortic rings to ACh and nitroprusside were measured. The expression of eNOS and NADPH oxidase subunits p47phox and p22phox in aortas were detected using Western blotting and immunohistochemistry. Aortic nitrotyrosine was measured with ELISA. The total antioxidant capacity (T-AOC) and MDA levels in aortas were also determined.
Results: The aortic rings of SHRs showed significantly smaller ACh-induced and nitroprusside-induced relaxation than those of control rats. Treatment of SHRs with sesamin increased both the endothelium-dependent and endothelium-independent relaxation of aortic rings in a dose-dependent manner. In aortas of SHRs, the level of T-AOC and the expression of nitrotyrosine, p22phox and p47phox proteins were markedly increased, while the level of MDA and the expression of eNOS protein were significantly decreased. Treatment of SHRs with sesamin dose-dependently reversed these biochemical and molecular abnormalities in aortas.
Conclusion: Long-term treatment with sesamin improves arterial function in SHR through the upregulation of eNOS expression and downregulation of p22phox and p47phox expression.
Keywords: sesamin; spontaneously hypertensive rat; aorta; vasorelaxation; endothelium; eNOS; NADPH oxidase; malondialdehyde; ACh; nitroprusside
This work was supported by grants from the Key Program of Natural Science Foundation of Education Department of Anhui Province (No 2006kj099A), the Program of Universities Excellent Young Talent Foundation of Anhui Province (No 2009SQRZ184) and the Young and Middle-aged Research Foundation of Wannan Medical College (No WK201206, WK201212).
* To whom correspondence should be addressed.
E-mail jryang1955@sina.com
Received 2012-09-06 Accepted 2013-01-11
Keywords:
Department of Pharmacology, Third-Grade Pharmacology Laboratory of State Administration of Traditional Chinese Medicine, Wannan Medical College, Wuhu 241001, China
Aim: Sesamin is one of the major lignans in sesame seeds with antihyperlipidemic, antioxidative and antihypertensive activities. The aim of this study was to examine the effects of sesamin on arterial function in spontaneously hypertensive rats (SHRs).
Methods: SHRs were orally administered sesamin (40, 80 and 160 mg·kg-1·d-1) for 16 weeks. After the rats were killed, thoracic aortas were dissected out. The vasorelaxation responses of aortic rings to ACh and nitroprusside were measured. The expression of eNOS and NADPH oxidase subunits p47phox and p22phox in aortas were detected using Western blotting and immunohistochemistry. Aortic nitrotyrosine was measured with ELISA. The total antioxidant capacity (T-AOC) and MDA levels in aortas were also determined.
Results: The aortic rings of SHRs showed significantly smaller ACh-induced and nitroprusside-induced relaxation than those of control rats. Treatment of SHRs with sesamin increased both the endothelium-dependent and endothelium-independent relaxation of aortic rings in a dose-dependent manner. In aortas of SHRs, the level of T-AOC and the expression of nitrotyrosine, p22phox and p47phox proteins were markedly increased, while the level of MDA and the expression of eNOS protein were significantly decreased. Treatment of SHRs with sesamin dose-dependently reversed these biochemical and molecular abnormalities in aortas.
Conclusion: Long-term treatment with sesamin improves arterial function in SHR through the upregulation of eNOS expression and downregulation of p22phox and p47phox expression.
Keywords: sesamin; spontaneously hypertensive rat; aorta; vasorelaxation; endothelium; eNOS; NADPH oxidase; malondialdehyde; ACh; nitroprusside
This work was supported by grants from the Key Program of Natural Science Foundation of Education Department of Anhui Province (No 2006kj099A), the Program of Universities Excellent Young Talent Foundation of Anhui Province (No 2009SQRZ184) and the Young and Middle-aged Research Foundation of Wannan Medical College (No WK201206, WK201212).
* To whom correspondence should be addressed.
E-mail jryang1955@sina.com
Received 2012-09-06 Accepted 2013-01-11