EFFECTS OF CHRONIC TREATMENT WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR OR AN ANGIOTENSIN RECEPTOR ANTAGONIST IN 2-KIDNEY, ONE-CLIP HYPERTENSIVE RATS

The effects of chronic angiotensin II (Ang II) receptor blockade (losartan) or converting enzyme inhibition (enalapril) on blood pressure (BP), urinary albumin excretion (UalbV), renal histology and the hemodynamic and excretory function of the clipped and nonclipped kidneys were studied in two-kidney, one-clip (2-K 1-C) rats. One day after clipping the right renal artery, male Wistar rats were divided into three groups receiving: (1) losartan, 20 mg/kg/day (N = 7), (2) enalapril, 20 mg/kg/day (N = 8), or (3) no treatment (controls, N = 9) for three weeks. Both losartan and enalapril treatments maintained conscious BP at comparably lowered levels compared to control animals (116 +/- 6 mm Hg and 113 +/- 2 mm Hg vs. 188 +/- 11 mm Hg, respectively, P < 0.01). Treatment also prevented the increase in UalbV, observed for the untreated group, three weeks after clipping (1.7 +/- 0.5 and 0.7 +/- 0.1 mg/24 hr vs. 17.5 +/- 7 mg/24 hr, respectively, P < 0.01). After three weeks of treatment, acute study of renal function during pentobarbital anesthesia revealed higher values of GFR and RPF and lowered vascular resistance for nonclipped kidneys from the losartan and enalapril groups compared to the corresponding kidneys from control animals. Despite the lower BP of both treated groups, clipped kidney GFR and RPF were unchanged compared to the control group. UalbV for nonclipped kidneys from untreated rats was approximately 5- to 10-fold higher than in the nonclipped kidneys from the treated groups. Histological evaluation revealed evidence of early glomerulosclerosis in the nonclipped kidneys from the untreated but not the treated groups, and decreased indices of glomerular size and mesangial expansion in clipped kidneys for the treated groups compared to the untreated group. These data support a primary role for Ang II modulation of blood pressure and renal function in the nonclipped kidney of the 2-K 1-C rat.