Renoprotective Effects of Benidipine in Combination with Angiotensin II Type 1 Receptor Blocker in Hypertensive Dahl Rats

DOI PubMed 被引用文献8件 参考文献42件
  • YAO Kozo
    Biomedical Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
  • SATO Hitoshi
    Toxicological Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
  • INA Yasuhiro
    Biomedical Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
  • SUZUKI Kazuo
    Toxicological Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
  • OHNO Tetsuji
    Biomedical Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
  • SHIRAKURA Shiro
    Biomedical Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.

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We examined the effects of the angiotensin II type 1 receptor blocker candesartan, the calcium channel blockers benidipine and amlodipine, hydralazine, and the combination of candesartan and benidipine or amlodipine on blood pressure and renal function in Dahl salt-sensitive (DS) hypertensive rats. Male DS rats (5 weeks of age) were fed a high-salt (8% NaCl) diet, resulting in hypertension accompanied by glomerular sclerosis and an increased urinary albumin excretion. Drugs were orally administered from 2 to 6 weeks after the start of the feeding. Although candesartan (1 or 10 mg/kg) had little effect on the blood pressure, benidipine (4 mg/kg), amlodipine (4 mg/kg) and hydralazine (5 mg/kg) had similar hypotensive effects. Benidipine, but not amlodipine, hydralazine, or candesartan, significantly inhibited the increase in the albuminuria and glomerular sclerosis. The combination of candesartan (1 mg/kg) and benidipine (4 mg/kg) lowered the levels of blood pressure and albuminuria more effectively than the combination of candesartan (1 mg/kg) and amlodipine (4 mg/kg). These results indicate that benidipine is effective in preventing the impairment of renal function in DS hypertensive rats, and suggest that additional benefits can be expected by combination therapy with benidipine and an angiotensin II type 1 receptor blocker. (Hypertens Res 2003; 26: 635-641)

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