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

The goal of the current study was to determine the mechanism by which doses of endothelin (ET) that do not markedly affect the glomerular filtration rate (GFR) cause a natriuresis and diuresis. ET was infused into pentobarbital-anesthetized female rats at 50 ng.kg-1.min-1 iv for 30 min. In controls (n = 6 rats; n = 5 in all other groups), ET increased mean arterial blood pressure (MAP) from 95 +/- 2 to 131 +/- 2 (SE) mmHg, Na excretion (UNa V) from 0.34 +/- 0.07 to 1.83 +/- 0.2 meq/min, and urine flow rate (V) from 13 +/- 1 to 24 +/- 3 ml/min (all P < 0.01 vs. baseline). At 15 min during infusion of ET, the GFR was not affected (2.1 +/- 0.1 to 2.2 +/- 0.1 ml/min) but modestly decreased to 1.8 +/- 0.1 ml/min at 30 min (P < 0.05 vs. baseline). Either removing the capsule from both kidneys during surgery or maintaining renal arterial pressure at baseline values with an adjustable clamp on the aorta above the right renal artery abolished the ET-induced increase in UNa V and V. Meclofenamate also did not alter the ET-induced increase in MAP, V, or UNa V. To determine the intrarenal site of action of ET, experiments were conducted with ET plus amiloride or with a combination of amiloride plus furosemide; there was a larger ET-induced diuresis and natriuresis in amiloride-treated rats and an even larger response with amiloride plus furosemide compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)