AIM: To investigate the role of the bradykinin(BK) B_2 receptor in the inhibitory effect of valsartan on
angiotensin Ⅱ(AngⅡ)-induced
cardiomyocyte hypertrophy.METHODS: Neonatal rat
cardiomyocytes were randomly divided into 6 groups: control,AngⅡ,valsartan,AngⅡ+valsartan,Hoe-140(a specific BK B_2 receptor antagonist) and AngⅡ+valsartan+Hoe-140.Flow cytometry(FCM) was used to evaluate the size and protein content of cardiomyocytes.Nitric oxide(NO) and intracellular cyclic GMP(cGMP) were measured by colorimetry and radioimmunoassay.RESULTS: 10~(-7)(mol·L~(-1)) AngⅡ significantly increased the size and protein content of cardiomyocytes compared to control(P<(0.01) for both),which was inhibited by 10~(-5)(mol·L~(-1)) valsartan(P<(0.01)).10~(-6)(mol·L~(-1)) Hoe-140 partially blocked the inhibitory effects of valsartan(P<(0.05) or P<(0.01) vs.AngⅡ+valsartan,respectively).In the Ang Ⅱgroup,NO was markedly decreased(P<(0.01) vs.control);valsartan significantly increased NO and intracellular cGMP compared to the Ang Ⅱgroup(P<(0.01) for both),and the effect of valsartan was attenuated by Hoe-140(P<(0.01) or P<(0.05) vs.Ang Ⅱ+valsartan,respectively).CONCLUSION: The BK B_2 receptor may partially mediate the antihypertrophic action of valsartan in Ang Ⅱ-induced cardiomyocyte hypertrophy,and the elevation of NO and cGMP may contribute to the cardioprotective effects of BK.