Adrenomedullin stimulates cAMP accumulation and inhibits atrial natriuretic peptide gene expression in cardiomyocytes.

Adrenomedullin (ADM) is a novel vasodilating and natriuretic peptide which may play an important role in cardiovascular regulation. In neonatal cardiomyocyte cultures we have shown that ADM leads to dose-dependent inceases in cAMP accumulation and subsequent inhibition of atrial natriuretic peptide (ANP) gene expression and secretion. Forskolin-mediated elevation of intracellular cAMP levels led to a qualitatively similar inhibitory effect on both ANP gene expression and secretion. These data show that ADM has direct effects on expression of ANP in the cardiomyocyte by a mechanism that may involve the activation of adenylate cyclase, lending further support to the hypothesis that ADM may act in vivo as an important endocrine or paracrine modulator of cardiovascular function.