Do kinins mediate cardioprotective and renoprotective effects of cilazapril in spontaneously hypertensive rats with renal ablation?
1. We assessed the potential of the kallikrein-kinin system in mediating the cardioprotective and renoprotective effects of an angiotensin-converting enzyme inhibitor (ACEI), cilazapril (CIL) in rats with renal ablation. 2. Eight week old spontaneously hypertensive rats (SHR) were subjected to 5/6 nephrectomy. One week after the operation, the rats were divided into 5 groups: (i) vehicle; (ii) CIL 1 mg/kg per day per os (p.o.); (iii) Hoe140 (HOE) 70 mu g/kg per day given intraperitoneally (i.p.); (iv) CIL 1 mg/kg per day p.o. plus HOE 7 mu g/kg per day i.p.; (v) CIL 1 mg/kg per day p.o. plus HOE 70 mu g/kg per day i.p. The treatment lasted for 4 weeks. 3. CIL alone significantly reduced systolic blood pressure, urinary protein excretion, heart weight and serum creatinine level. HOE alone did not induce any significant changes in these parameters. CIL in combination with HOE (7 or 70 mu g/kg per day) did not induce any changes in these parameters, in addition to those associated with the effects of CIL alone. 4. These results indicate that the kallikrein-kinin system might not play a major role in the cardioprotective and renoprotective effects of ACE inhibitors in the rat remnant kidney model of chronic renal failure.
Kohzuki
M
M
Section of Internal Medicine and Disability Prevention, Tohoku University Graduate School, Sendai, Japan.
Yasujima
M
M
Kanazawa
M
M
Yoshida
K
K
Sato
T
T
Abe
K
K
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000804:Angiotensin II / Q000096:biosynthesis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D017315:Cilazapril / Q000627:therapeutic use*; D006331:Heart Diseases / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000502:physiology; D007674:Kidney Diseases / Q000503:physiopathology / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000503:physiopathology; D007677:Kidney Function Tests; D007705:Kinins / Q000378:metabolism / Q000502:physiology*; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D000804:Angiotensin II; D017315:Cilazapril; C065679:icatibant; D001920:Bradykinin