Cardioprotective effects of NIP-121, a novel ATP-sensitive potassium channel opener, during ischemia and reperfusion in coronary perfused guinea pig myocardium

Author(s): Okazaki, K., Shigenobu, K.

Journal/Book: J Cardiovasc Pharmacol. 1996; 27: 227 East Washington Sq, Philadelphia, PA 19106. Lippincott-Raven Publ. 695-701.

Abstract: We investigated the effect of NIP-121, a novel ATP-sensitive K+ channel opener, on myocardial damage during ischemia/reperfusion. The action potential and contractile force of coronary-perfused guinea pig right ventricular walls were recorded. The preparations were subjected to 30-min no-flow ischemia with or without NIP-121 or glibenclamide, followed by 60-min reperfusion. In untreated tissues, decreases in action potential duration (APD) and contractile force and an increase in resting tension were observed during the no-flow period. On reperfusion, transient arrhythmias were observed and resting or contractile force returned to <50% of preischemic values. NIP-121, at 0.3 mu M, a concentration showing only a slight negative inotropic effect, caused a faster decrease in APD and contractile force but abolished the increase in resting tension (RT) during the no-flow period. On reperfusion, no arrhythmia was observed in NIP-121-treated preparations, and contractile force recovered to similar to 80% of the preischemic value. Glibenclamide 1 mu M attenuated the decrease in APD but affected neither the decrease in contractile force nor the increase in RT during the :no-flow period. On reperfusion, the incidence of arrhythmia was increased in glibenclamide-treated preparations, lions, and the recovery of basal tension and contractile force was inhibited: Contractile force recovered to only similar to 15% of the preischemic value. NIP-121 was also shown to attenuate the decrease in tissue ATP during ischemia and reperfusion. We demonstrated that NIP-121 may have protective effects against myocardial injury during ischemia and reperfusion. Activation of ATP-sensitive K+ current may be an adaptive mechanism for cardioprotection under compromised blood flow.

Note: Article H Tanaka, Toho Univ, Sch Pharmaceut Sci, Dept Pharmacol, Miyama 2-2-1, Chiba 274, Japan

Keyword(s): ischemia; reperfusion; K+ channel opener; NIP-121; glibenclamide; myocardial injury; guinea pigs; INTRACELLULAR SODIUM ACTIVITY; ACTION-POTENTIAL DURATION; RAT VENTRICULAR MYOCYTES; REGULATED K+ CHANNELS; CONTRACTILE FAILURE; HEART-CELLS; CROMAKALIM; DEPLETION; HYPOXIA; MUSCLE

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