Atrial natriuretic factor blocks the pressor action of endothelin

The present study was designed to determine the pharmacologic effects of rat atrial natriuretic factor (r-ANF; 250 ng/kg/min), endothelin-3 (ET-3; 340 ng/kg/min), and combined r-ANF and ET-3 infusion on cardiac hemodynamics and renal function in anesthetized rats. The change in mean arterial pressure (delta MAP) was 13 +/- 2 mm Hg during ET-3 infusion alone. Delta MAP was -9 +/- 2 mm Hg during r-ANF infusion alone. Combined infusion of ET-3 and r-ANF resulted in a change in MAP of -7 +/- 3 mm Hg. The decrease in MAP during combined infusion of ET-3 and r-ANF occurred due to a decrease in cardiac output. Infusion of r-ANF did not block the cardiac output. Infusion of r-ANF did not block the ET-3-induced increase in total peripheral resistance (TPR). Infusion of r-ANF alone resulted in an 11-fold increase in urinary sodium excretion. ET-3 infusion completely blocked the ANF-induced natriuresis in part by markedly decreasing the glomerular filtration rate (GFR). ET-3 or r-ANF infusion alone resulted in two- or eightfold increases, respectively, in circulating r-ANF levels compared to vehicle alone. However, combined infusion of r-ANF and ET-3 resulted in a dramatic 27-fold increase in circulating r-ANF when compared to levels obtained during vehicle infusion alone. The present study demonstrates that at pharmacologic levels, r-ANF blocks the pressor action of ET-3 by decreasing cardiac output rather than TPR. Furthermore, ET-3 blocks the natriuretic action of r-ANF, partly by decreasing GFR.