Benidipine inhibits apoptosis during ischaemic acute renal failure in rats.
We have investigated the effects of benidipine (hydrochloride), a calcium antagonist, against ischaemic acute renal failure in rats. Using histological examination, we studied whether the inhibition of apoptosis was associated with the protective effects of benidipine on the ischaemic renal injury. Acute renal failure was induced by the unilateral clamping of the left renal artery for 60 min, followed by reperfusion and contralateral nephrectomy. Drugs were given intravenously 5 min before the unilateral clamping. Prophylactic administrations of benidipine (10 microg kg(-1), i.v.) significantly ameliorated the development of renal failure as estimated by the measurements of serum creatinine and blood urea nitrogen 24 h after the reperfusion. Amlodipine (besilate, 100 and 300 microg kg(-1), i.v.) tended to attenuate renal dysfunction. Lisinopril (300 and 1000 microg kg(-1), i.v.), an angiotensin converting enzyme inhibitor, was ineffective in this acute renal failure model. Histological examination using the terminal transferase-mediated dUTP-biotin nick end-labelling (TUNEL) method to detect apoptotic cells revealed that the TUNEL-positive tubular epithelium was prominent in the renal cortex 24 h after the reperfusion. The TUNEL-positive cells were significantly reduced by pretreatment with benidipine. The results demonstrate that benidipine can ameliorate the ischaemic acute renal failure in rats and suggest that the renoprotective effect of benidipine was at least partly attributable to the reduction of apoptosis in tubular epithelial cells.
Yao
K
K
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd, Japan.
Sato
H
H
Ina
Y
Y
Nagashima
K
K
Nishikawa
S
S
Ohmori
K
K
Ohno
T
T
D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001806:Blood Urea Nitrogen; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C061004:benidipine; D003404:Creatinine