ADRENOMEDULLIN STIMULATES CAMP ACCUMULATION AND INHIBITS ATRIAL-NATRIURETIC-PEPTIDE GENE-EXPRESSION IN CARDIOMYOCYTES

Adrenomedullin (ADM) is a novel vasodilating and natriuretic peptide w hich may play an important role in cardiovascular regulation. In neona tal cardiomyocyte cultures we have shown that ADM leads to dose-depend ent increases in cAMP accumulation and subsequent inhibition of atrial natriuretic peptide (ANP) gene expression and secretion, Forskolin-me diated elevation of intracellular cAMP levels led to a qualitatively s imilar inhibitory effect on both ANP gene expression and secretion. Th ese data show that ADM has direct effects on expression of ANP in the cardiomyocyte by a mechanism that may involve the activation of adenyl ate cyclase, lending further support to the hypothesis that ADM may ac t in vivo as an important endocrine or paracrine modulator of cardiova scular function. (C) 1997 Academic Press