Statins and ACE Inhibitors Improve Vascular Dysfunction in Zucker Obese Rats

Abstract

Previous studies have shown vascular dysfunction in coronary, mesenteric and epineurial resistance arteries in Zucker obese rats, a model of the metabolic syndrome. Our hypothesis is that treatment with HMG-CoA reductase inhibitor (statin) or angiotension coverting enzyme (ACE) inhibitor (enalapril) will improve vascular dysfunction in Zucker obese rats. 20-week-old rats were treated with statin (50mg/Kg/day) or enalapril (40mg/Kg/day) for 10 weeks. We examined vascular dysfunction in 28 – 32 week old Zucker lean and Zucker obese rats (untreated and treated). We studied ventricular, mesenteric and epineurial vessels (75 – 175μm intraluminal diameter and ~1 mm in length) using an isolated vessel preparation. Vessels were studied under hydrostatic pressure (40mm Hg) and no flow, placed on an inverted microscope and diameter measured. Dilator responses were evaluated for acetylcholine (Ach, 10−10–10−4M), bradykinin (10−12–10−6M), and sodium nitroprusside (10−10–10−4M), after constriction with U46619. Results Endothelial dependent responses were attenuated in each vascular bed from Zucker obese rats (coronary, 10uM Ach = 60.8% decrease), (mesenteric, 1uM bradykinin = 65.4% decrease) and (epineurial, 10uM Ach = 41.4% decrease) compared to responses from lean rats. Responses to these agonists were augmented in vessels from Zucker obese rats treated with statin or enalapril, when compared to vessels from untreated rats. Our data suggest that endothelial dependent dysfunction is improved when Zucker obese rats were treated with statin or ACE inhibitor. Supported by VA Merits to Dr. Oltman and Dr. Yorek.