Yao Kozo, Sato Hitoshi, Ina Yasuhiro, Suzuki Kazuo, Ohno Tetsuji, Shirakura Shiro
Biomedical Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Hypertens Res. 2003 Aug;26(8):635-41. doi: 10.1291/hypres.26.635.
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.
我们研究了血管紧张素II 1型受体阻滞剂坎地沙坦、钙通道阻滞剂贝尼地平与氨氯地平、肼屈嗪以及坎地沙坦与贝尼地平或氨氯地平联合用药对 Dahl 盐敏感（DS）高血压大鼠血压和肾功能的影响。雄性 DS 大鼠（5 周龄）喂食高盐（8%氯化钠）饮食，导致高血压并伴有肾小球硬化和尿白蛋白排泄增加。从喂食开始后 2 至 6 周口服给药。尽管坎地沙坦（1 或 10 mg/kg）对血压影响很小，但贝尼地平（4 mg/kg）、氨氯地平（4 mg/kg）和肼屈嗪（5 mg/kg）具有相似的降压作用。贝尼地平而非氨氯地平、肼屈嗪或坎地沙坦能显著抑制蛋白尿增加和肾小球硬化。坎地沙坦（1 mg/kg）与贝尼地平（4 mg/kg）联合用药比坎地沙坦（1 mg/kg）与氨氯地平（4 mg/kg）联合用药更有效地降低血压和蛋白尿水平。这些结果表明贝尼地平对预防 DS 高血压大鼠肾功能损害有效，并提示贝尼地平与血管紧张素II 1型受体阻滞剂联合治疗有望带来额外益处。
