Cardioprotective effects of KRN2391 and nicorandil on ischemic dysfunction in perfused rat heart.
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.
Ohta
H
H
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Gunma, Japan.
Jinno
Y
Y
Harada
K
K
Ogawa
N
N
Fukushima
H
H
Nishikori
K
K
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D020108:Nicorandil; D010477:Perfusion; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000627:therapeutic use*
D011725:Pyridines; D014665:Vasodilator Agents; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D009536:Niacinamide; D020108:Nicorandil; D005905:Glyburide