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 (losa rtan) or converting enzyme inhibition (enalapril) on blood pressure (B P), urinary albumin excretion (UalbV), renal histology and the hemodyn amic and excretory function of the clipped and nonclipped kidneys were studied in two-kidney, one-clip (2-K 1-C) rats. One day after clippin g the right renal artery, male Wistar rats were divided into three gro ups receiving: (1) losartan, 20 mg/kg/day (N = 7), (2) enalapril, 20 m g/kg/day (N = 8), or (3) no treatment (controls, N = 9) for three week s. Both losartan and enalapril treatments maintained conscious BP at c omparably lowered levels compared to control animals (116 +/- 6 mm Hg and 113 +/- 2 mm Hg vs. 188 +/- 11 mm Hg, respectively, P < 0.01). Tre atment also prevented the increase in UalbV, observed for the untreate d 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 week s of treatment, acute study of renal function during pentobarbital ane sthesia revealed higher values of GFR and RPF and lowered vascular res istance for nonclipped kidneys from the losartan and enalapril groups compared to the corresponding kidneys from control animals. Despite th e lower BP of both treated groups, clipped kidney GFR and RPF were unc hanged compared to the control group. UalbV for nonclipped kidneys fro m untreated rats was approximately 5- to 10-fold higher than in the no nclipped kidneys from the treated groups. Histological evaluation reve aled evidence of early glomerulosclerosis in the nonclipped kidneys fr om the untreated but not the treated groups, and decreased indices of glomerular size and mesangial expansion in clipped kidneys for the tre ated groups compared to the untreated group. These data support a prim ary role for Ang II modulation of blood pressure and renal function in the nonclipped kidney of the 2-K 1-C rat.