Cardioprotective effects of nicorandil.

Abstract

The effects of nicorandil, a nicotinamide nitrate with K(+)-channel-opening activity, was investigated in several models of ischemia-reperfusion injury in conscious and anesthetized dogs or isolated buffer-perfused rat hearts. In several models of reversible ischemic injury (stunned myocardium) in dogs, nicorandil resulted in an enhanced recovery of regional systolic shortening during reperfusion after a single episode of coronary artery occlusion (10-15 min). These beneficial actions of nicorandil were not shared by the nitrovasodilator sodium nitroprusside but were mimicked by the selective K(+)-channel opener EMD 52692. In a model of irreversible ischemia-reperfusion injury (i.e., 2 h of coronary occlusion followed by reperfusion) in anesthetized dogs, nicorandil produced a marked reduction of myocardial infarct size. An equihypotensive dose of the calcium antagonist nifedipine had no significant effect; however, EMD 52692 produced the same reduction in infarct size as had nicorandil. In isolated, perfused rat hearts subjected to 20 min of low-flow (1.0 ml/min) global ischemia followed by 30 min of reperfusion, nicorandil (7 microM) resulted in a significant improvement in the recovery of isovolumic left ventricular minute work during reperfusion compared with untreated hearts. Finally, the results of in vitro experiments indicated that nicorandil (10(-6) to 10(-3) M) produced a concentration-dependent inhibition of superoxide anion free radical production by human and canine neutrophils. The K(+)-channel opener EMD 52692 also inhibited superoxide production in canine neutrophils. These results indicate that nicorandil is a highly efficacious myocardial protective agent in several animal models of reversible or irreversible ischemia-reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: G J Gross, J A Auchampach, M Maruyama, D C Warltier, G M Pieper
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 20 Suppl 3 Pg. S22-8 ( 1992) ISSN: 0160-2446 [Print] United States
• PMID: 1282172 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzopyrans
• Dihydropyridines
• Potassium Channels
• Superoxides
• Niacinamide
• Nicorandil
• bimakalim
• Nifedipine

Topics

• Animals
• Benzopyrans (pharmacology)
• Coronary Circulation (drug effects)
• Dihydropyridines (pharmacology)
• Dogs
• Female
• Heart (drug effects)
• In Vitro Techniques
• Male
• Myocardial Infarction (prevention & control)
• Myocardial Reperfusion Injury (drug therapy)
• Neutrophils (drug effects, physiology)
• Niacinamide (analogs & derivatives, pharmacology)
• Nicorandil
• Nifedipine (pharmacology)
• Potassium Channels (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reperfusion
• Superoxides (analysis)