KININ AND ANGIOTENSIN-II RECEPTOR ANTAGONISTS IN RATS WITH CHRONIC-RENAL-FAILURE - CHRONIC EFFECTS ON CARDIOPROTECTION AND RENOPROTECTION OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS

Objective: To assess the potential of the kallikrein-kinin and renin-a ngiotensin systems in mediating the cardio- and renoprotective effects of angiotensin converting enzyme (ACE) inhibitors in rats with chroni c renal failure. Materials and methods: Spontaneously hypertensive rat s (SHR) and normotensive control Wistar-Kyoto (WKY) rats subjected to five-sixths nephrectomy were randomly assigned to treatment with vehic le, a kinin antagonist (Hoe 140) or an ACE inhibitor (cilazapril) or b oth drugs, intraperitoneally via osmotic minipumps for 4 weeks. In add ition, the effects of a chronic infusion of a specific angiotensin rec eptor antagonist (losartan) alone or in combination with an ACE inhibi tor (enalapril) were also investigated in nephrectomized SHR for 2 wee ks.Results: In nephrectomized SHR and WKY rats, cilazapril alone signi ficantly reduced systolic blood pressure, urinary protein excretion, h eart weight and serum creatinine. In nephrectomized SHR, Hoe 140 alone or cilazapril in combination with Hoe 140 (7 or 70 mu g/kg per day) i nduced no changes in these parameters, other than those associated wit h the effects of cilazapril alone. In nephrectomized WKY rats, cilazap ril in combination with Hoe 140 (70 mu g/kg per day) slightly, but not significantly, attenuated the antihypertensive effect of cilazapril b ut did not affect the other parameters. These results were confirmed b y morphological analysis of kidneys. All the drug regimens provided ef fective protection against an increase in focal glomerular sclerosis. Enalapril did not modify the antihypertensive and renoprotective effec ts of losartan in nephrectomized SHR. Conclusions: The present results indicate that the kallikrein-kinin system might not be a major factor in the cardio- and renoprotective effects of ACE inhibitors in rats w ith chronic renal failure.