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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/H1264    most recent 00804.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Erdös, B. Articles by Busija, D. W. Search for Related Content PubMed PubMed Citation Articles by Erdös, B. Articles by Busija, D. W.

Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production

¹Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina; and ²Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary

Submitted 29 July 2005 ; accepted in final form 19 October 2005

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·kg^–1·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.

cerebral circulation; statins; nitric oxide; potassium channels; diabetes mellitus

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