Using the primary culture of neonatal rat ventricular myocytes, synthesis and secretion of rat atrial natriuretic peptide (rANP) were studied. Ventricular myocytes in culture, although contained less amounts of cellular immunoreactive (IR)-rANP, secreted substantial amounts of IR-rANP at a rate comparable to that of atrial myocytes. Dexamethasone markedly stimulated synthesis and secretion of IR-rANP by cultured ventricular myocytes in a dose-dependent manner (10(-10)-10(-6) M), of which effect was far more potent than that in atrial myocytes. Testosterone and triiodothyronine also stimulated synthesis and secretion of ventricular IR-rANP to the extent comparable to that of atrial IR-rANP. The present study suggests that tissue-dependent difference in glucocorticoids sensitivity plays an important role in the regulation of developmental ANP gene expression in mammalian heart.