Abstract: AIM: To investigate the role of the bradykinin (BK) B₂ receptor in the inhibitory effect of valsartan on angiotensin Ⅱ (Ang Ⅱ)-induced cardiomyocyte hypertrophy.METHODS: Neonatal rat cardiomyocytes were randomly divided into 6 groups:control, Ang Ⅱ, valsartan, Ang Ⅱ +valsartan, Hoe-140 (a specific BK B₂ receptor antagonist) and Ang Ⅱ +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 Ang Ⅱ 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.Ang Ⅱ +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 B₂ 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.

Key words: bradykinin, bradykinin B₂ receptor, valsartan, angiotensin Ⅱ, cardiomyocyte, NO, cGMP