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

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 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.

• Authors: H Tanaka, K Okazaki, K Shigenobu
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 27 Issue 5 Pg. 695-701 (May 1996) ISSN: 0160-2446 [Print] United States
• PMID: 8859940 (Publication Type: Journal Article)

Chemical References

• Oxadiazoles
• Piperidines
• Potassium Channels
• NIP 121
• Adenosine Triphosphate
• Glyburide

Topics

• Action Potentials (drug effects)
• Adenosine Triphosphate (analysis, pharmacology)
• Animals
• Glyburide (pharmacology)
• Guinea Pigs
• Myocardial Contraction (drug effects)
• Myocardial Ischemia (physiopathology)
• Myocardial Reperfusion Injury (prevention & control)
• Oxadiazoles (pharmacology)
• Piperidines (pharmacology)
• Potassium Channels (drug effects)