CHRONIC EFFECTS OF ENDOTHELIN-3 ON BLOOD-PRESSURE AND RENAL HEMODYNAMICS IN RATS

Background. Renal vasoconstriction and systemic hypertension are well- known effects of bolus or shortterm endothelin administration. However , the role of endothelin as a circulating hormone remains largely unkn own. Methods. The present study explores the effects of endothelin-3 ( ET-3) on renal haemodynamics and systemic blood pressure during a 3-h and a 3-day intravenous infusion in rats. Male Sprague-Dawley (SD) rat s were infused with vehicle (group 1) or ET-3 (group 2, 10 ng/kg per m in; group 3, 50 ng/kg per min) delivered via osmotic minipumps into th e right jugular vein for 3 days. On day 3 after pump implantation, rat s were anaesthetized with Inactin and surgically prepared for assessme nt of mean arterial blood pressure (MABP), renal plasma flow (RPF), gl omerular filtration rate (GFR), and renal vascular resistance (RVR). T he same parameters were assessed during a 3-h ET-3 infusion study in S D rats (group 4, vehicle; group 5, ET-3, 10 ng/kg per min; group 6, ET -3, 50 ng/kg per min). Results. In 3-day infused rats, ET-3 induced a significant decrease in RPF (-22+/-17% and -26+/-18% for group 2 and g roup 3 respectively, P<0.05 vs group 1) and an increase in RVR (+40+/- 11% for groups 2 and 3; P<0.05 vs group 1); 50 ng/kg per min ET-3 sign ificantly decreased GFR (-17%, P<0.05 vs group 1). MABP was not signif icantly affected by endothelin infusion. In acute infusion studies a d ecrease of the same magnitude was seen for the renal haemodynamics val ues. 50 ng/kg per min ET-3 increased MABP; a systemic effect that disa ppeared after the 3 day infusion. Conclusions. This study suggests tha t intravenously administered ET-3 in the rat has only a transient effe ct on systemic blood pressure, whereas it induces alterations in renal haemodynamics after both acute and chronic perfusions.