Positive inotropic action, natriuresis and atrial natriuretic factor release induced by endothelin in the conscious rat.
Endothelin is a novel endothelium-derived vasoconstrictor peptide. We investigated its effect on atrial natriuretic factor (ANF) release and on several cardiovascular and renal parameter, since ANF release is induced via hemodynamic changes in response to angiotensin II, another vasoconstrictor peptide. Male Sprague-Dawley rats were infused intravenously for 60 min with either saline or endothelin at 10, 50 or 100 ng/kg per min and then allowed to recover for 20 min. A third group was splenectomized 24 h before infusion with 100 ng/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 100 ng/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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Garcia
R
R
Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, Quebec, Canada.
Lachance
D
D
Thibault
G
G
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects*; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D016232:Endothelins; D014662:Vasoconstrictor Agents; C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor