Protective effects of benidipine against myocardial damage following ischemia and reperfusion in the isolated perfused rat heart.
We investigated the possible protective effects of benidipine (Coniel), a calcium antagonist, on mechanical dysfunction, metabolic damage and changes in vascular reactivity during ischemia and reperfusion in the Langendorff-perfused rat heart. The responses of perfusion pressure to U-46619, a vasoconstrictor, and acetylcholine, an endothelial-dependent vasodilator, were also determined as indices of the vascular function. Thirty min of reperfusion following 30 min of global ischemia produced contractile failure and the marked release of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK). Additionally, the ischemia and reperfusion augmented the vasoconstrictor response to U-46619, and depressed the endothelium-dependent vasodilator response to acetylcholine. These hearts were treated with 1 or 10 nM benidipine from 20 min before ischemia to the beginning of ischemia. While benidipine at 10 nM had a modest negative inotropic action, 1 nM of this drug had minimal depressant effects on the preischemic function. The depressed contractile function after the ischemia was improved, and the increased releases of LDH and CPK were significantly ameliorated by benidipine. Also, benidipine restored the augmented contractile response to U-46619 and preserved the vasodilator response to acetylcholine. These results demonstrate that pretreatment with benidipine prevents myocardial injury following ischemia and reperfusion. The cardioprotective effects of benidipine may in part be due to the protection of vascular reactivity by this drug.
Yao
K
K
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Karasawa
A
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; C061004:benidipine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine