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Cardioprotective effects of KRN2391 and nicorandil on ischemic dysfunction in perfused rat heart.

Abstract
The cardioprotective effect of KRN2391 (N-cyano-N-(2-nitroxymethyl)-3- pyridinecarboximidamide methanesulfonate), a novel vasodilator, was studied in the isolated perfused rat heart and compared with that of nicorandil. The isolated buffer-perfused rat heart was subjected to 25 min ischemia followed by 30 min reperfusion. The heart was pretreated with 0.1-10 microM KRN2391, 10-1000 microM nicorandil or vehicle. Before ischemia, KRN2391 (1-10 microM) and nicorandil (10-1000 microM) increased coronary flow, but did not modify the cardiac mechanical function. KRN2391 (1-10 microM) and nicorandil at high doses (300-1000 microM) resulted in significant improvements of cardiac functions and coronary flow during reperfusion and significantly reduced the release of cytosolic enzymes. The protective effects of 3 microM KRN2391 and 300 microM nicorandil were completely reversed by 3 microM glibenclamide, a blocker of ATP-sensitive potassium channels. Thus, KRN2391 and nicorandil at high doses have a direct cardioprotective effect, which may be related to activation of ATP-sensitive potassium channels.
AuthorsH Ohta, Y Jinno, K Harada, N Ogawa, H Fukushima, K Nishikori
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 204 Issue 2 Pg. 171-7 (Nov 05 1991) ISSN: 0014-2999 [Print] Netherlands
PMID1839621 (Publication Type: Journal Article)
Chemical References
  • Pyridines
  • Vasodilator Agents
  • N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate
  • Niacinamide
  • Nicorandil
  • Glyburide
Topics
  • Animals
  • Coronary Disease (drug therapy, physiopathology)
  • Cytosol (drug effects, enzymology)
  • Glyburide (pharmacology)
  • Heart Rate (drug effects)
  • In Vitro Techniques
  • Male
  • Myocardium (enzymology)
  • Niacinamide (analogs & derivatives, antagonists & inhibitors, therapeutic use)
  • Nicorandil
  • Perfusion
  • Pyridines (antagonists & inhibitors, therapeutic use)
  • Rats
  • Rats, Inbred Strains
  • Vasodilator Agents (therapeutic use)

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