Role of kinins in the renoprotective effect of angiotensin-converting enzyme inhibitors in experimental chronic renal failure.
The aim of this study was to investigate whether the renoprotective effect of angiotensin-converting enzyme inhibitors (ACEIs) following 5/6 renal mass reduction is due in part to the potentiation of kinins. Three groups of rats with 5/6 renal mass reduction were studied during the 14 weeks following surgery. One group received no therapy (control); the second group was treated from the beginning with the ACEI ramipril (1 mg/kg/day) added to the drinking water, and the last group received ramipril plus a beta2-bradykinin antagonist, HOE 140 (500 microg/kg/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 ramipril 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 (initial 11.6+/-2.0 and final 38.9+/-11 mg/ 24 h). The systolic blood pressure of the controls increased from 106+/-2 to 144+/-5 mm Hg at the 14th week. Ramipril abolished the increase in systolic blood pressure. The effect of ramipril was reverted by HOE 140 (initial 108+/-2 and final 140+/-9 mmHg). Control rats had more severe histopathologic changes. Those animals receiving ramipril + HOE 140 displayed less severe glomerular changes, while rats treated only with ramipril had mild alterations. 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+/-1,410, 19,693+/-2,200 and 14,352+/-3,200 microm2, respectively, for the 3 groups. These results suggest that the protective effect of ACEIs in the development of chronic renal failure is partially mediated by kinins.
MacLaughlin
M
M
Instituto de Investigaciones Cardiológicas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Monserrat
A J
AJ
Muller
A
A
Matoso
M
M
Amorena
C
C
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D007705:Kinins / Q000378:metabolism*; D017257:Ramipril / Q000008:administration & dosage*; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007705:Kinins; C065679:icatibant; D017257:Ramipril; D001920:Bradykinin