Protection by benidipine hydrochloride (KW-3049), a calcium antagonist, of ischemic kidney in rats via inhibitions of Ca-overload, ATP-decline and lipid peroxidation.
Renal failure was produced in rats by unilateral clamping of the left renal artery for 60 min, followed by reperfusion and contralateral nephrectomy. Prophylactic administrations of benidipine (10, 30 micrograms/kg, i.v.) significantly ameliorated the development of renal failure as estimated by histological examination as well as by the measurements of serum creatinine and blood urea nitrogen. ATP content of the ischemic kidney dropped immediately after renal ischemia, and this decline persisted for more than 48 hr after reperfusion. The content of lipid peroxide in the kidney was increased 15 min after reperfusion following renal ischemia. Calcium content of the kidney progressively increased after reperfusion and reached the peak level 24 hr after reperfusion, whereas calcium content scarcely changed during 60 min of renal ischemia. The decline of ATP, the lipid peroxidation, and the increase in calcium content of the kidney observed after reperfusion were significantly inhibited by pretreatment of the rats with benidipine (30 micrograms/kg, i.v.). These results suggest that lipid peroxidation and Ca-overload play causative roles in the pathogenesis of acute ischemic renal failure and that benidipine protects the ischemic kidney by inhibiting these deteriorating consequences.
Karasawa
A
A
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Kubo
K
K
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001806:Blood Urea Nitrogen; D002118:Calcium / Q000633:toxicity*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D007511:Ischemia; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*
D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D000255:Adenosine Triphosphate; D003404:Creatinine; D009543:Nifedipine; D002118:Calcium