Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production
Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production
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DOI：
10.1152/ajpheart.00804.2005
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发表时间：
2006-03-01
影响因子：
4.8
通讯作者：
Busija, DW
中科院分区：
文献类型：
--
作者：
Erdös, B;Snipes, JA;Busija, DW
胰岛素抵抗会导致脑血管功能障碍，增加中风的风险。我们研究了瑞舒伐他汀（RSV），一种3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，是否可以逆转胰岛素抵抗大鼠脑血管反应性降低。在麻醉的12周龄胰岛素抵抗Zucker肥胖（ZO）和瘦（ZL）大鼠中，通过颅窗制备，检查1天或4周RSV（2 mg中心点kg（-1）中心点d（-1））治疗后基底动脉（BA）的扩张反应。与ZL大鼠相比，溶剂处理的ZO大鼠具有显著更高的空腹胰岛素、总胆固醇（TC）和甘油三酯（TG）水平。此外，在ZO大鼠中，与ZL大鼠相比，BA对乙酰胆碱、伊洛前列素、克罗卡林和氯化钾的扩张反应显著降低。一天的RSV治疗改善了ZO BA的扩张反应，而不改变脂质水平。4周RSV治疗使TC和TG均降低30%，并且还改善了ZO BA的扩张反应，尽管与1天RSV治疗相比没有额外的作用。与ZL大鼠相比，赋形剂处理的ZO大鼠的脑动脉中NAD（P）H氧化酶依赖性超氧化物的产生显著更高，但1天和4周RSV处理均使ZO动脉中超氧化物水平升高正常化。这些结果表明，RSV改善胰岛素抵抗的脑血管功能独立于其通过抑制NAD（P）H氧化酶的降脂作用。
Insulin-resistance induces cerebrovascular dysfunction and increases the risk for stroke. We investigated whether rosuvastatin (RSV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, can reverse reduced cerebrovascular responsiveness in insulin-resistant rats. Dilator responses of the basilar artery ( BA) were examined after 1-day or 4-wk RSV (2 mg center dot kg(-1) center dot day(-1)) treatment in anesthetized 12-wk-old insulin-resistant Zucker obese (ZO) and lean (ZL) rats by using a cranial window preparation. Vehicle-treated ZO rats had significantly higher fasting insulin, total cholesterol (TC), and triglyceride (TG) levels compared with ZL rats. In addition, in the ZO rats, dilator responses of the BA to acetylcholine, iloprost, cromakalim, and potassium chloride were significantly reduced when compared with ZL rats. One-day RSV treatment improved dilator responses of the ZO BAs without altering lipid levels. Four-week RSV treatment lowered both TC and TG by 30% and also improved dilator responses of the ZO BAs, although without additional effects compared with the 1-day RSV treatment. NAD(P)H oxidase-dependent superoxide production was significantly higher in the cerebral arteries of vehicle-treated ZO rats compared with ZL rats, but both 1-day and 4-wk RSV treatments normalized elevated superoxide levels in the ZO arteries. These findings demonstrate that RSV improves cerebrovascular function in insulin-resistance independently from its lipid-lowering effect by the inhibition of NAD( P) H oxidase.