Enalapril Inhibits Growth and Proliferation of Various Tissues in Rat Normotensive Four–Sixths Kidney Ablation Nephropathy

Abstract

Most experimental studies on kidney proliferation and its attenuation by angiotensin–converting enzyme inhibitors were performed in the rat hypertensive remnant–kidney model with a five–sixths kidney ablation. The developing hypertension rose the objections on the hypertension and its treatment in control rats. A normotensive four–sixths remnant–kidney model (Nx) was elaborated, compared with sham–operated (S) animals, and a subantihypertensive dosage of enalapril (E) was administered for 4 weeks of intensive kidney tissue proliferation (NxE). The pair–fed groups increased their body weight and blood pressure comparably. Moderately increased plasma creatinine and urea concentrations were found in the Nx group; markedly increased levels in the 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 tubular 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 remarkably (NxE 15.3±10.5 vs. Nx 26.2 ±10.8), but E did not inhibit the Col accumulation. 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 protein/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 increased the Col concentration in muscle (NxE 141±3 vs. Nx 110±5 mg/100 g, p<0.01), while it attenuated the increase in protein/DNA ratio (NxE 36.6±2.1 vs. Nx 66.3±4.7, p<0.01). In conclusion, kidney ablation nephropathy stimulating kidney proliferation evokes only minor changes in heart, liver and striated muscle. E inhibits markedly 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 borderline.