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Circulation Journal
Vol. 71 (2007) No. 10 p. 1622-1628

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http://doi.org/10.1253/circj.71.1622

Experimental Investigation

Background Statins reportedly protect against myocardial infarction, but the precise mechanism is unclear. Methods and Results Rabbits underwent 30 min of coronary occlusion followed by 48 h of reperfusion. Pravastatin (1 or 5 mg/kg) or saline was intravenously administered 10 min before ischemia. Pravastatin (5 mg/kg) was also administered 10 min before reperfusion. Nω-nitro-L-arginine methylester (L-NAME, 10 mg/kg), chelerythrine (5 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD, 5 mg/kg) was intravenously administered 10 min before pravastatin injection. The infarct size was determined. The myocardial interstitial levels of 2,5-dihydroxybenzoic acid (DHBA) and nitrogen oxide (NOx), and the intensity of myocardial dihydroethidium staining were measured. Pre-ischemic treatment with pravastatin reduced the infarct size (34±5% and 24±4%, 1 and 5 mg/kg, respectively), but not pre-reperfusion treatment (42.1±3.7%), compared with the control (45±3%). This effect was blocked by L-NAME (42.6±4%), chelerythrine (50.9±3%) and 5-HD (52.7±2%). Pre-ischemic treatment with pravastatin increased myocardial NOx levels, and attenuated both the 2,5-DHBA level and the intensity of dihydroethidium staining during reperfusion. Chelerythrine abolished the increase in NOx levels by pravastatin. Conclusion Pre-ischemic treatment with pravastatin reduces the myocardial infarct size via protein kinase C-dependent nitric oxide production, decreasing hydroxyl radicals and superoxide, and opening the mitochondrial adenosine triphosphate-sensitive potassium channels. (Circ J 2007; 71: 1622 - 1628)

Copyright © 2007 THE JAPANESE CIRCULATION SOCIETY

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