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Am J Physiol Regul Integr Comp Physiol (March 25, 2004). doi:10.1152/ajpregu.00647.2003
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Submitted on November 4, 2003
Accepted on March 17, 2004

Rosuvastatin Treatment Reverses Impaired Coronary Artery Vasodilation in Fructose-fed, Insulin Resistant Rats

Allison W Miller*, D. Pharm, Christina D Tulbert, and David W Busija1

1 Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

* To whom correspondence should be addressed. E-mail: amiller{at}wfubmc.edu.

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 HMG-CoA 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 one week, rats received rosuvastatin (2mg/kg) or placebo (saline) subcutaneously for 5 weeks. 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 as compared to other groups. Rosuvastatin treatment of FF rats normalized TG and modestly decreased insulin levels. Acetylcholine (ACh) induced dilator responses were depressed in arteries from FF-placebo rats. This impairment was due to decreased responses via calcium-dependent K channels (KCa). 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 KCa. Thus, rosuvastatin treatment of IR rats normalizes coronary vascular dilator responses by improving the KCa function.




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