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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

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

Narentuoya Bao, Shinya Minatoguchi, Hiroyuki Kobayashi, Shinji Yasuda, Itta Kawamura, Masamitsu Iwasa, Takahiko Yamaki, Syohei Sumi, Yu Misao, Masazumi Arai, Kazuhiko Nishigaki, Genzou Takemura, Takako Fujiwara, etc.

Circ J. 2007 Oct;71(10):1622-8.

PMID: 17895562

Abstract:

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. N(omega)-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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP71186533	5-Hydroxydecanoic acid sodium salt		71186-53-3	Price

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