Pravastatin reduces myocardial infarct size via increasing protein kinase C-dependent nitric oxide, decreasing oxyradicals and opening the mitochondrial adenosine triphosphate-sensitive potassium channels in rabbits

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 (I or 5 mg/kg) or saline was intravenously administered 10 min before ischemia. Pravastatin (5 mg/kg) was also administered 10min before reperfusion. N-omega-nitro-L-arginine methylester (L-NAME, 10mg/kg), chelerythrine (5mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD, 5mg/kg) was intravenously administered 10min before pravastatin injection. The infarct size was determined. The myocardial interstitial levels of 2,5dihydroxybenzoic 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.