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1 Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC, USA; Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary
2 Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC, USA
* To whom correspondence should be addressed. E-mail: dbusija{at}wfubmc.edu.
Insulin-resistance induces cerebrovascular dysfunction and increases the risk for stroke. We investigated if rosuvastatin (RSV), an HMG-CoA 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-week RSV (2 mg/kg/day) treatment in anesthetized 12-wk-old insulin-resistant Zucker obese (ZO) and lean (ZL) rats using a cranial window preparation. Vehicle-treated ZO rats had significantly higher fasting insulin, total cholesterol (TC), and triglyceride (TG) levels compared to ZLs. In addition, in the ZO rats, dilator responses of the BA to acetylcholine, iloprost, cromakalim and potassium chloride were significantly reduced compared to ZLs. 1-day RSV improved dilator responses of the ZO BAs without altering lipid levels. 4-wk RSV lowered both TC and TG by 30%, and also improved dilator responses of the ZO BAs, although without additional effects compared to 1-day RSV. NAD(P)H-oxidase-dependent superoxide production was significantly higher in the cerebral arteries of vehicle treated ZO rats compared to ZLs, but both 1-day and 4-wk RSV 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.
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