The Effects of a Newly Synthesized ATP-Sensitive Potassium Channel Opener, MJ-355, on Blood Pressure and Myocardial Ischemia-Reperfusion Injury in Rats

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Author(s)

Abstract

ATP-sensitive potassium (K<SUB>ATP</SUB>) channel openers, exerting a potent vasodilatory 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-<I>trans</I>-3, 4-dihydro-2, 2-dimethyl-2<I>H</I>-3-hydroxy4-[2-oxo-5<I>S</I>-(1-ethoxyethoxymethyl)-1-pyrrolidinyl]-1-benzopyran), a newly synthesized K<SUB>ATP</SUB> channel opener, on hemodynamics in spontaneously hypertensive rats and on myocardial ischemia-reperfusion injury in a rat model of 45 min left coronary artery occlusion followed by 1-h reperfusion. Intravascular 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 ventricular premature contractions and ventricular tachycardia, total duration of ventricular fibrillation and the mortality. Additionally, a significant reduction in infarct size was noted in all of the MJ-355-treated groups. The hemodynamic and cardioprotective effects of MJ-355 were virtually abolished by pretreating the rats with glibenclamide (4 mg/kg, i.v. bolus), a selective K<SUB>ATP</SUB> channel blocker. In conclusion, MJ-355, through the activation of K<SUB>ATP</SUB> 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.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 81(2), 185-193, 1999-10

    The Japanese Pharmacological Society

References:  28

Codes

  • NII Article ID (NAID)
    10008196835
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4886668
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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