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 fi ltration rate (GFR) cause a natriuresis and diuresis. ET was infused i nto 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 increa sed mean arterial blood pressure (MAP) from 95 +/- 2 to 131 +/- 2 (SE) mmHg, Na excretion (U(Na)V) from 0.34 +/- 0.07 to 1.83 +/- 0.2 meq/mi n, 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 af fected (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 t he capsule from both kidneys during surgery or maintaining renal arter ial pressure at baseline values with an adjustable clamp on the aorta above the right renal artery abolished the ET-induced increase in U(Na )V and V. Meclofenamate also did not alter the ET-induced increase in MAP, V, or U(Na)V. To determine the intrarenal site of action of ET, e xperiments 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. Finally, as a c ontrol for the decapsulation procedure, amiloride alone resulted in si milar increases in V and U(Na)V in intact rats as in rats without rena l capsules. Our data indicate that ET-induced natriuresis and diuresis are arterial blood pressure-related phenomena (pressure natriuresis a nd diuresis) resulting from an inhibition of sodium reabsorption proxi mal to the thick ascending limb and that changes in prostaglandin synt hesis are not involved.