Chronic effects of endothelin-3 on blood pressure and renal haemodynamics in rats

BACKGROUND.: Renal vasoconstriction and systemic hypertension are well-knowneffects of bolus or short-term endothelin administration. However,the role of endothelin as a circulating hormone remains largelyunknown. METHODS.: The present study explores the effects of endothelin-3 (ET-3)on renal haemodynamics and systemic blood pressure during a3-h and a 3-day intravenous infusion in rats. Male Sprague-Dawley(SD) rats were infused with vehicle (group 1) or ET-3 (group2, 10 ng/kg per min; group 3, 50 ng/kg per min) delivered viaosmotic minipumps into the right jugular vein for 3 days. Onday 3 after pump implantation, rats were anaesthetized withInactin and surgically prepared for assessment of mean arterialblood pressure (MABP), renal plasma flow (RPF), glomerular filtrationrate (GFR), and renal vascular resistance (RVR). The same parameterswere assessed during a 3-h ET-3 infusion study in SD rats (group4, 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 inRPF (–22±7% and –26±8% for group 2and group 3 respectively, P<0.05 vs group 1) and an increasein RVR (+40±11% for groups 2 and 3; P<0.05 vs group1); 50 ng/kg per min ET-3 significantly decreased GFR (–17%,P<0.05 vs group 1). MABP was not significantly affected byendothelin infusion. In acute infusion studies a decrease ofthe same magnitude was seen for the renal haemodynamics values.50 ng/kg per min ET-3 increased MABP; a systemic effect thatdisappeared after the 3-day infusion. CONCLUSIONS.: This study suggests that intravenously administered ET-3 inthe rat has only a transient effect on systemic blood pressure,whereas it induces alterations in renal haemodynamics afterboth acute and chronic perfusions.