Pravastatin attenuates cardiovascular inflammatory and proliferative changes in a rat model of chronic inhibition of nitric oxide synthesis by its cholesterol-lowering independent actions

Kensuke Egashira, Weihua N.I. Ni, Shujiro Inoue, Chu Kataoka, Shiro Kitamoto, Masamichi Koyanagi, Akira Takeshita

研究成果: Contribution to journalArticle査読

34 被引用数 (Scopus)

抄録

Recent studies suggest that some of the beneficial effects of 3-hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitors such as pravastatin may be through their cholesterol-lowering independent effects on the blood vessels. We have recently reported that chronic inhibition of nitric oxide (NO) synthesis with N(ω)-nitro-L-arginine methyl ester (L-NAME) increases systolic blood pressure and induces coronary vascular inflammatory changes in rats. We designed this study to investigate whether treatment with pravastatin attenuates such proarteriosclerotic changes through their cholesterol-lowering independent effects. Several groups of Wistar-Kyoto rats were studied: the control group, L group received L-NAME in their drinking water (100 mg/kg per day) and L + Px group received L-NAME plus pravastatin (50, 100 or 250 mg/kg per day). We observed marked increases in monocyte infiltration into the coronary arteries, proliferative cell nuclear antigen-positive cells, and monocyte chemoattractant protein-1 (MCP-1) expression in the heart on day 3 after L-NAME administration began. Treatment with pravastatin did not affect serum cholesterol levels or systolic blood pressure but did reduce the L-NAME induced inflammatory and proliferative changes. Pravastatin also attenuated the MCP-1 gene expression induced by L-NAME. In summary, pravastatin inhibited the inflammatory and proliferative changes in the coronary vessels through their cholesterol-independent effects in this model, which may provide an insight into the mechanisms of anti-inflammatory or anti-arteriosclerotic actions of pravastatin.

本文言語英語
ページ(範囲)353-358
ページ数6
ジャーナルHypertension Research
23
4
DOI
出版ステータス出版済み - 7 2000

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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