Enalapril in subantihypertensive dosage attenuates kidney proliferation and functional recovery in normotensive ablation nephropathy of the rat

Most studies on the antiproliferative action of angiotensin converting enzy me inhibitors (ACEI) were performed in a rat hypertensive remnant kidney mo del with 5/6 kidney ablation which raised objections about the antihyperten sive effect of ACEI and the influence of other antihypertensive drugs admin istered to remnant kidney control rats. To prevent these objections, a norm otensive 4/6 remnant kidney model was elaborated and a subantihypertensive dosage of enalapril was used to evaluate its antiproliferative action. Subt otally nephrectomized rats (Nx) markedly increased the remnant kidney weigh t during a 4-week period and this rise was prevented by the treatment with enalapril (NxE) (Nx +297+/-35 mg vs. sham-operated +145+/-32 mg, p<0.001; N xE +154+/-35 mg vs. Nx p<0.001). While collagen concentration in the kidney cortex was not increased in sham-operated rats (Sham) in comparison with t he control group (Ctrl) at the beginning of the study, the subsequent incre ase was significant in the Nx group and enalapril did not attenuate this in crease (Sham 148+/-5 mg/100 g w.w. vs. Nx 164+/-2 mg/100 g w.w., p<0.01;NxE 161+/-4 mg/100 g w.w. vs. Sham p<0.05). The tubular protein/DNA ratio incr ease, which was significant in the Nx group, was inhibited by enalapril (Nx 26.2+/-10.5 vs. NxE 15.3+/-2.6, p<0.05). The protein/DNA ratio was much lo wer in glomeruli, with no significant changes in either the Nx or NxE group s. Serum urea concentrations were slightly higher in the Nx group than in t he sham-operated group, but markedly elevated in the NxE group (Nx 10.7+/-0 .76 mmol/l vs. Sham 6.10+/-0.33 mmol/l, p<0.001; NxE 28.9+/-2.6 mmol/l vs. Sham p<0.001). Creatinine concentrations in the Nx group were increased in comparison with the sham-operated group and markedly increased in the NxE g roup (Nx 63.7+/-3.56 mu mol/l vs. Sham 37.2+/-2.84 mu mol/l, p<0.001; NxE 1 07.0+/-5.2 mu mol/l vs. Sham p<0.001). The clearance of creatinine was lowe r in the Nx group than in the sham-operated group and was markedly reduced in the NxE group (Nx 0.89+/-0.06 ml/min.g kidney wt, vs. Sham 1.05+/-0.16 m l/min.g kidney wt., p<0.01; NxE 0.58+/-0.029 ml/min.g kidney wt. vs. Sham, p<0.001). Enalapril improved proteinuria in comparison with the Nx group (N xE 5.6+/-0.6 mg/24 h vs. Nx 16.1+/-3.4 mg/24 h, p<0.05). Thus remnant kidne y proliferation is substantial even in normotensive rats. It includes both proliferation and collagen accumulation with partial recovery of kidney wei ght and function, but is accompanied by enhanced proteinuria. Enalapril att enuates the proliferation and decreases proteinuria but prolongs kidney fun ction recovery.