The effect of angiotensin II receptor antagonists on kidney function in two-kidney, two-clip Goldblatt hypertensive rats.

The effect of blockade of the renin-angiotensin system on kidney function using non-peptide angiotensin AT1 receptor antagonists was investigated in renovascular hypertensive rats. An angiotensin converting enzyme inhibitor, captopril and two angiotensin AT1 receptor antagonists, losartan and GR138950 (1-([3-bromo-2[2-[[(trifluoro-methyl)sulphonyl]amino]phenyl]-5 benzofuranyl]methyl)-4-cyclopropyl-2-ethyl-1H-imidazole-5-carboxamide) were administered in Na+-deplete two-kidney, two-clip Goldblatt hypertensive rats over a 3-day period. Captopril, losartan (30 mg/kg body weight) and GR138950 (5 mg/kg body weight) significantly (P < 0.001) 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 pressure in these three groups of rats was similar and occurred with comparable marked increases in plasma levels of urea and creatinine indicative of acute renal failure. These findings demonstrate an important role for angiotensin II in the maintenance of renal function during blood pressure reduction in renovascular hypertensive states during restriction of dietary Na+ intake.