DEXAMETHASONE-INDUCED UP-REGULATION OF ADRENOMEDULLIN AND ATRIAL-NATRIURETIC-PEPTIDE GENES IN CULTURED RAT VENTRICULAR MYOCYTES

To determine whether adrenomedullin (AM), a novel 51-residue vasodilat or peptide originally isolated from human pheochromocytoma, is express ed by the heart, and whether the expression of cardiac AM gene is regu lated by glucocorticoids, the effect of dexamethasone (DEX) on the exp ression of protein and mRNA of AM and atrial natriuretic peptide (ANP) was tested in cultured ventricular myocytes prepared from the neonata l rats. Northern blot analysis of rat ventricular myocytes with cDNAs for rat AM and ANP as probes revealed distinct bands corresponding to the sizes of rat AM mRNA (1.6 kb) and rat ANP mRNA (1 kb), respectivel y. Dexamethasone increased steady-state levels of both AM and ANP mRNA as well as secretion of both AM and ANP immunoreactivity in a time-an d dose-dependent manner, The stimulatory effects of dexamethasone were completely abolished by a glucocorticoid antagonist (RU38486 and a RN A synthesis inhibitor (actinomycin D), The approximate half-lives of b asal and dexamethasone-induced AM mRNA were about 4 h, suggesting that dexamethasone-induced up-regulation of AM mRNA was unlikely due to it s decreased degradation. These data suggest that glucocorticoids direc tly stimulate gene expression of AM as well as ANP in rat ventricular myocytes. (C) 1997 Academic Press Limited.