Cardioprotective effects of NIP-121, a novel ATP-sensitive potassium channel opener, during ischemia and reperfusion in coronary perfused guinea pig myocardium.
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 microM, 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 approximately 80% of the preischemic value. Glibenclamide 1 microM 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, and the recovery of basal tension and contractile force was inhibited: Contractile force recovered to only approximately 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.
Tanaka
H
H
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan.
Okazaki
K
K
Shigenobu
K
K
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010069:Oxadiazoles / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*
D010069:Oxadiazoles; D010880:Piperidines; D015221:Potassium Channels; C070366:NIP 121; D000255:Adenosine Triphosphate; D005905:Glyburide