Renoprotective effects of benidipine in combination with angiotensin II type 1 receptor blocker in hypertensive Dahl rats.
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.
Biomedical Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan. kozo.yao@kyowa.co.jp
Kozo
K
Yao
Hitoshi
H
Sato
Yasuhiro
Y
Ina
Kazuo
K
Suzuki
Tetsuji
T
Ohno
Shiro
S
Shirakura
D000419:Albuminuria / Q000188:drug therapy / Q000473:pathology; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004095:Dihydropyridines / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D013777:Tetrazoles / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D013777:Tetrazoles; C061004:benidipine; D003404:Creatinine; C081643:candesartan