Low doses of endothelin-1 inhibit atrial natriuretic peptide secretion

To clarify the interaction between endothelin-1 (ET-1) and atrial natriuretic peptide (ANP), the effects of ET-1 on ANP secretion were investigated in isolated perfused rat hearts and in conscious unrestrained rats. Perfusion with 10(-9) M ET-1 stimulated ANP secretion from the isolated perfused rat heart. However, 10(-10) M ET-1 significantly decreased ANP secretion for the initial 15 min of the perfusion period. The perfusion with 10(-11) M ET-1, which is near the plasma level of ET-1 (2 x 10(-12) M), inhibited ANP secretion throughout the perfusion period. The perfusion of 10(-12) M ET-1 slightly decreased ANP secretion. After the ET-1 perfusion period, ANP secretion increased in proportion to ET-1 dose. The inhibitory action of ET-1 on ANP secretion was almost abolished by simultaneous perfusion of indomethacin, a cyclooxygenase inhibitor, but not by methylene blue, an inhibitor of soluble guanylate cyclase. In conscious unrestrained rats the iv infusion of 1 pmol/kg.min ET-1, which doubled the plasma...