Enalapril inhibits growth and proliferation of various tissues in rat normotensive four-sixths kidney ablation nephropathy

Most experimental studies on kidney proliferation and its attenuation by an giotensin-converting enzyme inhibitors were performed in the rat hypertensi ve remnant-kidney model with a five-sixths kidney ablation. The developing hypertension rose the objections on the hypertension and its treatment in c ontrol rats. A normotensive four-sixths remnant-kidney model (Nx) was elabo rated, compared with sham-operated (S) animals, and a subantihypertensive d osage of enalapril (E) was administered for 4 weeks of intensive kidney tis sue proliferation (NxE). The pair-fed groups increased their body weight an d blood pressure comparably. Moderately increased plasma creatinine and ure a concentrations were found in the Nx group; markedly increased levels in t he NxE group. Nx increased proteinuria, and E attenuated its increase. The remnant-kidney weight (Nx 912+/-31 vs. S 1,111+/-36 mg, p<0.001) was still lower, but collagen (Col; Nx 164+/-2 vs. S 148+/-5 mg/100 g, p<0.05) and tu bular protein/DNA ratio (Nx 26.2+/-10.8 vs. S 9.8+/-1.0, p<0.05) increased markedly in the Nx group; E attenuated the kidney growth (NxE 719+/-31 vs. Nx 912+/-31 mg, p<0.01) and decreased the tubular protein/DNA ratio remarka bly (NxE 15.3+/-10.5 vs. Nx 26.2 +/-10.8), but E did not inhibit: the Col a ccumulation. Nx decreased the heart (Nx 1,002+/-28 vs. S 1,130+/-41 mg, p<0 .05), but not liver weights and did not influence Col concentrations or pro tein/DNA ratios either in heart or liver. E potentiated the weight decrease of heart (NxE 862+/-20 vs. Nx 1,002+/-28 mg, p<0.01) and liver (NxE 8.3+/- 0.44 vs. Nx 10.3+/-0.51 g, p<0.001) and Col accumulation (heart: NxE 113+/- 6 vs. Nx 92+/-5 mg/100 g, p<0.01; liver: NxE 134+/-8 vs. Nx 101+/-9 mg/100 g, p<0.01). Nx did not influence either the soleus muscle weight or its Col accumulation, but it increased its protein/DNA ratio (Nx 66.3+/-4.7 vs. S 35.5+/-2.8 mg/100 g, p<0.01). E in creased the Col concentration in muscle (NxE 141+/-3 vs. Nx 110+/-5 mg/100 g, p<0.01), while it attenuated the incr ease in protein/DNA ratio (NxE 36.6+/-2.1 vs. Nx 66.3+/-4.7, p<0.01). In co nclusion, kidney ablation nephropathy stimulating kidney proliferation evok es only minor changes in heart, liver and striated muscle. E inhibits marke dly the kidney proliferation and functional recovery, but does not prevent the Col accumulation. E evokes antiproliferative changes also in the heart and surprisingly even in the liver. Alterations in soleus muscle are only b orderline. Copyright (C) 2000 S. Karger AG, Basel.