Angiotensin II Upregulation of Cardiomyocyte Adiponectin Production Is Nitric Oxide/Cyclic GMP Dependent

作者:Guo, Bingyan; Li, Yongjun*; Han, Rui; Zhou, Hong; Wang, Mei
来源:American Journal of the Medical Sciences, 2011, 341(5): 350-355.
DOI:10.1097/MAJ.0b013e318203abd5

摘要

Introduction: Adiponectin is a circulating cytokine that is now known to be synthesized by cardiomyocytes. Accumulating evidence has shown that adiponectin production is upregulated in patients with heart failure, with activation of the renin-angiotensin system and increased formation of angiotensin (Ang) II playing a critical role in left ventricular remodeling and heart failure. To determine whether Ang II upregulates adiponectin in hypertrophic cardiomyocytes, the authors need to explore the underlying mechanisms that could be involved. Methods: To test this hypothesis, neonatal rat ventricular myocytes (NRVMs) were treated with various concentrations of Ang II, and adiponectin expression was measured by quantitative real-time reverse transcription-polymerase chain reaction and Western immunoblotting. Results: Adiponectin mRNA expression was significantly increased by Ang II at concentrations from 10(-6) to 10(-8) M and was increased in a time-dependent manner at concentrations of 10(-7) M. Angiotensin type-2 receptor activation is required for Ang II-stimulated effects on adiponectin. A nitric oxide synthase inhibitor (Nx-nitro-L-arginine methyl ester hydrochloride) and an analog of cGMP antagonist (Rp-8-Br-CGMP-S) blocked Ang II-mediated upregulation of adiponectin. Conclusions: These data suggest a mechanism whereby Ang II upregulates adiponectin in NRVMs via the angiotensin type-2 receptor/nitric oxide/cGMP/protein kinase G signaling pathway.