ROLE OF KININS IN THE RENOPROTECTIVE EFFECT OF ANGIOTENSIN-CONVERTINGENZYME-INHIBITORS IN EXPERIMENTAL CHRONIC-RENAL-FAILURE

The aim of this study was to investigate whether the renoprotective ef fect of angiotensin-converting enzyme inhibitors (ACEIs) following 5/6 renal mass reduction is due in part to the potentiation of kinins. Th ree groups of rats with 5/6 renal mass reduction were studied during t he 14 weeks following surgery. One group received no therapy (control) ; the second group was treated from the beginning with the ACEI ramipr il (1 mg/kg/day) added to the drinking water, and the last group recei ved ramipril plus a beta(2)-bradykinin antagonist, HOE 140 (500 mu g/k g/day) via osmotic minipumps. Plasma creatinine did not change in any group during the study. Urinary protein excretion rose in the controls from 9.18+/-1.6 to 45.0+/-5.6 mg/24 h at the end of the study. In ram ipril group proteinuria was prevented (initial 7.5+/-1.0 and final 8.6 +/-0.8 mg/24h). The effect of ramipril was abolished by HOE 140 (initi al 11.6+/-2.0 and final 38.9+/-11 mg/ 24h). The systolic blood pressur e of the controls increased from 106+/-2 to 144+/-5 mmHg at the 14th w eek. Ramipril abolished the increase in systolic blood pressure. The e ffect of ramipril was reverted by KOE 140 (initial 108+/-2 and final 1 40+/-9 mmHg). Control rats had more severe histopathologic changes. Th ose animals receiving ramipril + HOE 140 displayed less severe glomeru lar changes, while rats treated only with ramipril had mild alteration s. Thus the glomerular injury score was 2.11+/-0.32 for controls, 1.53 +/-0.52 for rats treated with ramipril + HOE 140, and 0.06+/-0.04 for rats treated only with ramipril. The glomerular area was 20,886+/-1,41 0, 19,693+/-2,200 and 14,352+/-3,200 mu m(2), respectively, for the 3 groups. These results suggest that the protective effect of ACEIs in t he development of chronic renal failure is partially mediated by kinin s.