THE EFFECT OF ANGIOTENSIN-II RECEPTOR ANTAGONISTS ON KIDNEY-FUNCTION IN 2-KIDNEY, 2-CLIP GOLDBLATT HYPERTENSIVE RATS

The effect of blockade of the renin-angiotensin system on kidney funct ion using non-peptide angiotensin AT, receptor antagonists was investi gated in renovascular hypertensive rats. An angiotensin converting enz yme inhibitor, captopril and two angiotensin AT, receptor antagonists, losartan and GR13895O -2[2-[[(trifluoro-methyl)sulphonyl]amino]phenyl ]-5 benzofuranyl] methyl)-4-cyclopropyl-2-ethyl-1H -imidazole-5-carbox amide) were administered in Na+-deplete two-kidney, two-clip Goldblatt hypertensive rats over a S-day period. Captopril, losartan (30 mg/kg body weight) and GR138950 (5 mg/kg body weight) significantly (P < 0.0 01) lowered the systolic blood pressure in the hypertensive rats from 290 +/- 5, 252 +/- 9 and 238 +/- 13 mmHg to 152 +/- 17, 148 +/- 9 and 123 +/- 6 mmHg, respectively. The magnitude of reduction in blood pres sure in these three groups of rats was similar and occurred with compa rable marked increases in plasma levels of urea and creatinine indicat ive of acute renal failure. These findings demonstrate an important ro le for angiotensin II in the maintenance of renal function during bloo d pressure reduction in renovascular hypertensive states during restri ction of dietary Na+ intake. (C) 1997 Elsevier Science B.V.