Endothelin is a potent secretagogue for atrial natriuretic peptide in cultured rat atrial myocytes.

Using cultured neonatal rat atrial cardiocytes, we have studied the effect of synthetic porcine endothelin (pET), a novel potent vasoconstrictor isolated from endothelial cells, on the release of immunoreactive (IR) rat atrial natriuretic peptide (rANP). pET stimulated IR-rANP secretion in a dose-dependent manner (10(-10)-10(-7) M) with an approximate half-maximally stimulatory dose of 2 x 10(-10) M. The pET-induced IR-rANP secretion was attenuated by Ca2+-channel blocker nicardipine, but no further stimulation was induced when combined with a Ca2+-channel agonist BAY-K 8644. pET in combination with tetradecanoyl-phorbol-acetate resulted in a synergistic effect on IR-rANP secretion. These data suggest that ET may play as an endogenous secretagogue for rANP by modulating Ca2+ influx through the voltage-dependent Ca2+-channels in atrial cardiocytes.