NATRIURETIC EFFECT OF NON-PRESSOR DOSES OF ENDOTHELIN-1 IN CONSCIOUS DOGS

1. Renal, endocrine and haemodynamic responses to separate intravenous infusions of three doses of endothelin-1 (40, 400 and 4000 fmol kg(-1 ) min(-1)) were investigated in conscious dogs. 2. Administration of 4 0, 400 and 4000 fmol kg(-1) min(-1) endothelin-1. for 120 min increase d plasma endothelin-1 levels by two-, seven- and 250-fold, respectivel y. 3. The two low doses did not have measurable effects on mean arteri al blood pressure and heart rate but tended to increase glomerular fil tration rate. The high dose increased mean arterial blood pressure (MA BP; from 104 +/- 4 to 138 +/- 4 mmHg, P < 0.05) and decreased heart ra te (from 71 +/- 4 to 46 +/- 3 beats min(-1), P < 0.05) as well as glom erular filtration rate (from 47 +/- 3 to 19 +/- 5 mi min(-1), P < 0.05 ). 4. At rates of 40 and 400 fmol kg(-1) min(-1), endothelin-1 increas ed sodium excretion about five- and eightfold, respectively Relative c hanges in fractional sodium excretion were very similar. The high dose was markedly antinatriuretic (reducing sodium excretion from 8.3 +/- 1.1 to 1.2 +/- 0.2 mu mol min(-1), P < 0.05). 5. Diuresis increased du ring the administration of the two lower doses, which did not change p lasma atrial natriuretic peptide or vasopressin concentrations. Urine flow increased after termination of the infusion of the presser dose d espite elevated plasma vasopressin and subnormal glomerular filtration rate. 6. Infusion of endothelin-1 at 40 fmol kg(-1) min(-1) did not c hange the concentrations of angiotensin II and atrial natriuretic pept ide in plasma. Infusion of 400 fmol kg(-1) min(-1) was associated with a decrease in plasma angiotensin II, while plasma atrial natriuretic peptide was unchanged. The high dose of endothelin-1 markedly increase d plasma levels of both hormones. 7. It is concluded that endothelin-1 at low plasma concentrations increases sodium excretion while a highe r presser dose of endothelin-1 is antinatriuretic. However, increases in plasma endothelin-1 seem to elicit diuresis over a wide concentrati on range, although possibly by different mechanisms.