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Nitric oxide/cyclic GMP pathway mediates the endothelin-1-upregulation of adiponectin expression in rat cardiomyocytes.

ABSTRACT: Endothelin-1 (ET-1) serves an important role in the development of cardiac dysfunction and heart failure. ET-1 and angiotensin II (AngII) comprise a mutually reciprocal signalling network in the myocardium and serve similar or additive roles in the development of heart failure. Our previous study previously demonstrated that AngII upregulated the expression of APN in cardiomyocytes through an AngII receptor type 2/nitric oxide (NO)/cyclic GMP(cGMP)-dependent pathway. The purpose of the present study was to determine the effects of ET-1 and the additive effects of ET-1 and AngII on the gene expression and secretion of APN, and the underlying mechanisms involved. ELISA was used to determine the secretion of adiponectin (APN) and reverse transcription-quantitative polymerase chain reaction was used to evaluate the gene expression of APN. ET-1 induced APN secretion in a time- and dose-dependent manner, and induced APN secretion with AngII simultaneously, as determined via APN mRNA analyses. ETA and ETB receptors were also involved. The use of a NO synthase inhibitor and an analogue of cGMP antagonist resulted in a diminished ET-1- and/or AngII-mediated APN induction in cardiomyocytes. These results suggested that ET-1, as well as AngII, upregulated the gene expression and secretion of APN via the common NO/cGMP-mediated mechanism.

SUBMITTER: Guo B

PROVIDER: S-EPMC5543422 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Levels of nitric oxide metabolites, adiponectin and endothelin are associated with SNPs of the adiponectin and endothelin genes.

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