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.
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Authors | H Ohta, Y Jinno, K Harada, N Ogawa, H Fukushima, K Nishikori |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 204
Issue 2
Pg. 171-7
(Nov 05 1991)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 1839621
(Publication Type: Journal Article)
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Chemical References |
- Pyridines
- Vasodilator Agents
- N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate
- Niacinamide
- Nicorandil
- Glyburide
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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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