Objectives We have demonstrated previously that angiotensin (Ang) II may upregulate adiponectin expression in hypertrophic cardiomyocytes via the angiotensin type-2 receptor/nitric oxide/cGMP signalling pathway. In this study, we further examined the combined effect of endothelin (ET)-1 and Ang II on adiponectin gene expression and secretion.
Methods neonatal rat ventricular myocytes (NRVMs) were treated with various concentrations of Ang II and (or) ET-1, adiponectin expression was measured by qPCR. Adiponectin release was measured by enzyme-linked immuosorbent assay.
Results ET-1 and Ang II induced adiponectin release in a synergistic manner that can be attributed to their synergistic induction of adiponectin gene expression, as evidenced by adiponectin mRNA analysis. Both ETA and ETB receptors seem to be involved. A nitric oxide synthase inhibitor (Nx-nitro-Larginine methyl ester hydrochloride) and an analogue of cGMP antagonist (Rp-8-Br-CGMP-S) also partly blocked ET-1 -mediated up regulation of adiponectin.
Conclusions ET-1 and Ang II may boost adiponectin secretion in a synergistic manner, probably through their synergistic induction of adiponectin gene expression in NRVMs. A commom mechanism via the nitric oxide/cGMP/protein kinase G signalling pathway may be involved.