Endogenous BNP attenuates cardiomyocyte hypertrophy induced by Ang II via p38 MAPK/Smad signaling.

Abstract

Previous studies suggest that B-type natriuretic peptide (BNP) exerts inhibitory effects on cardiac hypertrophy. Our studies have shown that long-term treatment of rats with BNP attenuated cardiac hypertrophy via down-regulation of TGF-β1 and up-regulation of smad7. However, the mechanisms have not been fully elucidated. In the present study, we examined the role of endogenous BNP on cardiomyocyte hypertrophy and the related molecular mechanisms. Cardiomyocytes from neonatal rats were cultured and a cardiomyocyte hypertrophy model was established with angiotensin II (Ang II). The effects of blockade of endogenous BNP by its receptor antagonist, HS-142-1, on cell hypertrophy were investigated. Cardiomyocyte hypertrophy indices, including cell surface area, protein content and [3H] incorporation were measured. Smad and mitogen-activated protein kinase (MAPK) protein expressions were detected using Western blot analysis. We found that HS-142-1 increased Ang II-stimulated cardiomyocyte hypertrophy and Smad activation. In addition, the increase of cardiomyocyte hypertrophy and the activation of Smad caused by HS-142-1 were not altered by the ERK inhibitor, PD98059, but were decreased by the p38 MAPK inhibitor, SB203580. These results demonstrate that endogenous BNP attenuates cardiomyocyte hypertrophy, and this may be mediated through p38 MAPK/Smad, but not ERK/Smad signaling pathway.