Endothelin-induced natriuresis and diuresis are pressure dependent events in the rat

Abstract

Doses of endothelin-1 (ET) that do not markedly affect the glo- merular filtration rate (GFR) cause a natriuresis and diuresis. The goal of the current study was to determine the mechanism by which endothelin induces this renal action. ET was infused into pentobar- bital anesthetized female rats, i.v., at 50 ng kg-1 min-1 for 30 min. In Group I (controls, n=6; n=5 in all other groups), Et increased mean arterial blood pressure (MAP) from 95+2 (mean+SE) to 131+2 mmHg, Na excretion (UNaV) from 0.34+0.07 to 1.83+02 Eq/min and urine flow rate (V) from 13+1 to 24+3 1/min (all p[.01 vs baseline). At 15 min during infusion of ET, the GFR was not affected (2.1+0.1 ml/min) but modestly decreased to 1.8+0.1 ml/min at 30 min (p[.05 vs baseline). To determine to what extent an intact renal capsule is required for ET-induced natriuresis and diuresis, the capsule was removed from both kidneys during surgery (Group II) and to what extent increases in renal arterial pressure contribute to ET-induced natriuresis and diuresis, this variable was fixed at the baseline value by means of an adjustable clamp positioned on the aorta above the exit of the right renal artery (Group III); in both of these experiments the ET-induced increases in UNaV and V were abolished. To determine to what extent prostaglandins are involved in ET-induced natriuresis and diuresis, experiments (Group IV) with meclofenamate (5 mg bolus injec- tion) were performed; meclofemamate did not alter the ET-induced inc- rease in MAP, V or UNaV. To determine the intrarenal site of action of ET, experiments were conducted with ET plus amiloride (0.3 mg/kg bolus followed by 0.04 mg kg-1 min-1) (Group V) or with a combination of amiloride + furosemide (0.8 mg/kg bolus followed by 0.1 mg kg-1 min-1) (Group VI); there was a larger ET-induced diuresis and natriu- resis in amiloride-treated rats and an even larger response with ami- loride + furosemide compared to controls. Finally, as a control for the decapsulation procedure, amiloride alone (0.2 mg bolus followed by 0.02 mg/min for 45 min) resulted in similar increases in V and UNaV in intact rats (Group VII) and in rats without renal capsules (Group VIII).