Key result
In nephrectomized rats, cilazapril significantly reduced blood pressure and proteinuria, and adding a kinin antagonist did not modify these effects, suggesting kinins are not major mediators.
Why the study?
Does the kallikrein-kinin system mediate the cardio- and renoprotective effects of ACE inhibitors in rats with chronic renal failure?
RCT
randomly assigned
Does the kallikrein-kinin system mediate the cardio- and renoprotective effects of ACE inhibitors in rats with chronic renal failure?
The kallikrein-kinin system does not appear to be a major mediator of the cardio- and renoprotective effects of ACE inhibitors in a rat model of chronic renal failure.
Kinins do not mediate ACEI effects in this rat CRF model; leaves open human translation and alternative mechanisms.
OBJECTIVE: To assess the potential of the kallikrein-kinin and renin-angiotensin systems in mediating the cardio- and renoprotective effects of angiotensin converting enzyme (ACE) inhibitors in rats with chronic renal failure. MATERIALS AND METHODS: Spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats subjected to five-sixths nephrectomy were randomly assigned to treatment with vehicle, a kinin antagonist (Hoe 140) or an ACE inhibitor (cilazapril) or both drugs, intraperitoneally via osmotic minipumps for 4 weeks. In addition, the effects of a chronic infusion of a specific angiotensin receptor antagonist (losartan) alone or in combination with an ACE inhibitor (enalapril) were also investigated in nephrectomized SHR for 2 weeks. RESULTS: In nephrectomized SHR and WKY rats, cilazapril alone significantly reduced systolic blood pressure, urinary protein excretion, heart 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) induced no changes in these parameters, other than those associated with the effects of cilazapril alone. In nephrectomized WKY rats, cilazapril in combination with Hoe 140 (70 mu g/kg per day) slightly, but not significantly, attenuated the antihypertensive effect of cilazapril but did not affect the other parameters. These results were confirmed by morphological analysis of kidneys. All the drug regimens provided effective protection against an increase in focal glomerular sclerosis. Enalapril did not modify the antihypertensive and renoprotective effects 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 with chronic renal failure.
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Kohzuki et al. (1995) conducted an RCT in chronic renal failure. ACE inhibitor (cilazapril) with or without kinin antagonist (Hoe 140) vs. vehicle was evaluated on systolic blood pressure, urinary protein excretion, heart weight and serum creatinine. In nephrectomized rats, cilazapril significantly reduced blood pressure and proteinuria, and adding a kinin antagonist did not modify these effects, suggesting kinins are not major mediators.
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