Positive inotropic action, natriuresis and atrial natriuretic factor release induced by endothelin in the conscious rat

Publisher Website
Google Scholar
Abstract
Endothelin is a novel endothelium-derived vasoconstrictor peptide. We investigated its effect on atrial natriuretic factor (ANF) release and on several cardiovascular and renal parameters, since ANF release is induced via hemodynamic changes in response to angiotensin II, another vasoconstrictor peptide. Male Sprague-Dawley rats were infused intravenously for 60min with either saline or endothelin at 10, 50 or 100ng/kg per min and then allowed to recover for 20 min. A third group was splenectomized 24 h before infusion with 100ng/kg per min endothelin. Mean arterial, left ventricular end-diastolic and central venous pressures (dP/dtmax), heart rate, plasma ANF-(1-98) concentration, urinary volume, urinary sodium excretion and hematocrit were evaluated. Mean arterial pressure was elevated by both medium and high endothelin doses, and with the high dose this elevation was sustained beyond the infusion period. No increases in either left ventricular end-diastolic or central venous pressures were observed at any dose level. In fact, in rats infused with 100 ng endothelin there was a progressive decline in central venous pressure and a raised hematocrit, even in the splenectomized group, suggesting a loss of plasma volume. All three dose levels elevated the dP/dtmax at different infusion times. The heart rate was not modified by any endothelin dose. Despite the decreased central venous pressure and unaltered left ventricular end-diastolic pressure, the 100ng/kg per min endothelin infusion induced a threefold increase in plasma ANF levels; these were correlated with changes in the dP/dtmax (r=0.49, P<0.05). Both 50 and 100ng/kg per min endothelin produced a decline in urinary volume and urinary sodium excretion, but this was significant only at the higher dose. The non-pressor dose of endothelin (10ng/kg per min) tended to increase diuresis, and significantly enhanced natriuresis. We conclude that increases in ANF induced by endothelin are not mediated by changes in atrial pressure, but could be evoked either by a direct stimulatory effect on cardiocytes or by increased cardiac contractility. Also, the possible role of impaired renal function induced by the higher dose of endothelin cannot be disregarded. The natriuretic response to low endothelin doses could be secondary to a vasodilatory action of the peptide on the renal vasculature