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LOCAL CONTROL OF CIRCULATION

Rosuvastatin treatment reverses impaired coronary artery vasodilation in fructose-fed, insulin-resistant rats

Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157

Submitted 4 November 2003 ; accepted in final form 17 March 2004

Insulin resistance (IR) impairs vascular responses in coronary arteries, but mechanisms of dysfunction and approaches to treatment remain unclear. We examined the ability of a new 3-hydroxy-methylglutaryl coenzyme A reductase inhibitor, rosuvastatin, to reverse reduced dilator responses in rats made IR by feeding a fructose-rich diet (FF). Sprague-Dawley rats were randomized to control (normal rat diet) or FF. After 1 wk, rats received rosuvastatin (2 mg/kg) or placebo (saline) subcutaneously for 5 wk. Biochemical measurements and in vitro functional studies of small coronary arteries were performed. Fasting insulin and triglyceride (TG) levels were markedly increased in FF-placebo rats compared with other groups. Rosuvastatin treatment of FF rats normalized TG and modestly decreased insulin levels. ACh-induced dilator responses were depressed in arteries from FF-placebo rats. This impairment was due to decreased responses via calcium-dependent K channels (K_Ca). Rosuvastatin treatment of FF rats completely reversed the response to ACh to normal levels. Moreover, this recovery in function was due to an improvement in vasodilation via K_Ca. Thus rosuvastatin treatment of IR rats normalizes coronary vascular dilator responses by improving the K_Ca function.

fructose-fed rat; insulin resistance; coronary arteries; calcium-dependent potassium channels

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