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 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.
Gajdos
M
M
Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic. gajdos@upkm.sk
Krivosíková
Z
Z
Sebeková
K
K
Lajdová
I
I
Spustová
V
V
Dzúrik
R
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004656:Enalapril / Q000494:pharmacology*; D006321:Heart / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D007674:Kidney Diseases / Q000473:pathology* / Q000503:physiopathology; D007677:Kidney Function Tests; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D009392:Nephrectomy; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D004247:DNA