Close correlation of the cardioprotective effect of FK409, a spontaneous NO releaser, with an increase in plasma cyclic GMP level.
FK409 ((+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide) , which has been reported by us to be a new spontaneous nitric oxide (NO) releaser, prevented myocardial infarction following occlusion and reperfusion in rat coronary artery and increased plasma cyclic GMP level in rats, dose-dependently and significantly at 32 mg kg-1. Isosorbide dinitrate (ISDN), which is the most popular orally active NO donor used in the treatment of ischaemic cardiovascular diseases, did not show significant effects at 32 mg kg-1 in either experiment. Therefore, it is suggested that FK409 can attenuate myocardial injury during ischaemia and reperfusion in contrast to ISDN and a change in plasma cyclic GMP level may serve as an indicator of the cardioprotective effect of NO-releasing drugs.
Kita
Y
Y
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Sugimoto
T
T
Hirasawa
Y
Y
Yoshida
K
K
Maeda
K
K
D000818:Animals; D006152:Cyclic GMP / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D009574:Nitro Compounds / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000627:therapeutic use*
D009574:Nitro Compounds; D014665:Vasodilator Agents; D009569:Nitric Oxide; C061872:FK 409; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate