Combined effects of benidipine and diltiazem in a rat model of experimental angina.
We examined the combined effects of the calcium channel blockers 1,4-dihydropyridine (benidipine) and benzothiazepine (diltiazem) on vasopressin-induced myocardial ischemia in anesthetized rats, an experimental model of angina. Benidipine (3, 10 microg/kg, i.v.) and diltiazem (300, 1000 microg/kg, i.v.) caused dose-related inhibition of vasopressin-induced S-wave depression, an index of myocardial ischemia. Co-administration of low doses of benidipine (3 microg/kg) and diltiazem (300 microg/kg) almost completely inhibited the S-wave depression, where the efficacy was similar to that obtained with the use of high doses of benidipine (10 microg/kg) or diltiazem (1000 microg/kg). These results suggest that the administration strategy employed may be useful in the treatment of angina pectoris.
Yao
Kozo
K
Biomedical Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Sunto, Shizuoka 411-8731, Japan. kozo.yao@kyowa.co.jp
Shirakura
Shiro
S
D000787:Angina Pectoris / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001127:Arginine Vasopressin; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014662:Vasoconstrictor Agents
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C061004:benidipine; D004110:Diltiazem