The effects of a newly synthesized ATP-sensitive potassium channel opener,MJ-355, on blood pressure and myocardial ischemia-reperfusion injury in rats

ATP-sensitive potassium (K-ATP) channel openers, exerting a potent vasodila tory action, are useful in the treatment of cardiovascular disorders; e.g., hypertension and angina pectoris. This study was designed to evaluate the effect of MJ-355 (6-cyano-3,4-trans-3, 4-dihydro-2,2-dimethyl-2H-3-hydroxy- 4-[2-oxo-5S(1-ethoxyethoxymethyl)-1-pyrrolidinyl]-1-benzopyran), a newly sy nthesized K-ATP channel opener, on hemodynamics in spontaneously hypertensi ve rats and on myocardial ischemia-reperfusion injury in a rat model of 45 min left coronary artery occlusion followed by 1-h reperfusion. Intravascul ar injection of MJ-355 (0.005, 0.05 and 0.1 mg/kg) produced a dose-related reduction in mean arterial blood pressure. The depressor effect started 10- 15 min after the administration and persisted for more than 3 h and was not accompanied by a reflex tachycardia. In myocardial ischemia, pretreatment of MJ-355 (0.02 mg/kg) significantly reduced the total number of ventricula r premature contractions and ventricular tachycardia, total duration of ven tricular fibrillation and the mortality. Additionally, a significant reduct ion in infarct size was noted in all of the MJ-355-treated groups. The hemo dynamic and cardioprotective effects of MJ-355 were virtually abolished by pretreating the rats with glibenclamide (4 mg/kg, i.v. bolus), a selective KATP channel blocker. In conclusion, MJ-355, through the activation of K-AT P channels, exhibited antihypertensive and cardioprotective effects. It is suggested that MJ-355 should be useful in the treatment of hypertension and /or acute myocardial infarction.