Effect Of Grape Seed Procyanidins On Improving Aortic Remodeling In Spontaneous Hypertensive Rats And Its Mechanisms

Objective: To investigate the effect of grape seed procyanidins(GSP)on improving aortic remodeling in spontaneous hypertensive rats(SHR)and to explore its possible mechanisms.Methods: 24 male SHR(8-week-old)were randomly divided into 4 groups(n=6 each group): SHR group,low dose GSP group(GSP-low,50 mg·kg-1·d-1,n=6),high dose GSP group(GSP-high,200 mg ·kg-1·d-1,n=6),captopril group(captopril,30 mg·kg-1·d-1,n=6).6 wistar Kyoto rats(8-week-old)were served as negative control group(WKY,n=6).According to the experimental groups,the rats were administered intragastrically with corresponding dose of GSP,captopril or distilled water for 6 weeks.Tail systolic pressure(SBP)of the rats in each gruop was measured by tail culf method every week.After 6 weeks,media cross-sectional area(MCSA),lumen area(LA)and MCSA/LA of thoracic aorta were assayed and calculated after HE staining.Collagen volume fraction(CVF)was examined by Masson staining.ELISA was performed to determine the collagen type I(COL I)and collagen type III(COL III)contents in thoracic aorta.Biochemical techniques were used to assay the catalase(CAT)activity,malondiadehyde(MDA)and nitric oxide(NO)contents in thoracic aorta.Western blot and immunohistochemistry(IHC)were used to detect the expression of endothelin-1(ET-1),B cell lymphoma/leukemia 2(Bcl-2),cysteine aspastic acid-specific protease 3(Caspase-3)and extracellular signal-regulated kinase1/2(ERK1/2)in thoracic aorta respectively.Results: Compared with WKY group,SBP in one to 6 weeks,MCSA,MCSA/LA,CVF,COL I,COL III and MDA contents,the expression of ET-1,Bcl-2 and ERK1/2 in thoracic aorta were significantly increased in SHR group(P<0.05,P<0.01),but LA,NO content,CAT activity and the expression of Caspase-3 of thoracic aorta were markedly decreased(P<0.01).The wall of thoracic aorta is thickened,the luminal is stenosis.A large number of collagen is deposition between smooth muscle,arranged in disorder.Compared with SHR group,GSP could significantly decrease the SBP(3 to 6 weeks,P<0.01),MCSA(P<0.01),MCSA/LA(P<0.01),CVF(P<0.01,except low dose GSP group),COL I(P<0.01,except low dose GSP group),COL III(P<0.01)and MDA contents(P<0.01,except low dose GSP group),the expression of ET-1(P<0.01,except low dose GSP group),Bcl-2 and ERK1/2 in thoracic aorta,increase the LA(P<0.01,except low dose GSP group),NO content,CAT activity(P<0.01,except low dose GSP group)and the expression of Caspase-3(P<0.01,except low dose GSP group),relieve collagen deposition and the thickeness of vascular wall.The treatment effect of high dose GSP group is most equivalent to the captopril group.Conclusion: These data suggest that GSP has an improving effect on thoracic aorta remodeling in SHR through lowering the SBP,the expression of ET-1,ERK1/2 and Bcl-2 in thoracic aorta,increasing the antioxidative ability,NO production and the quantity of Caspase-3 protein.