Improvement of endothelial function in insulin-resistant carotid arteries treated with pravastatin

Object. Insulin resistance and hypertension are independent risk factors fo r stroke. Endothelial dysfunction in response to risk factors and carotid a rtery (.CA.) disease are important in the pathogenesis of stroke. Pravastat in may have cholesterol-independent pleiotropic effects. In the present stu dy the authors examined the effects of short-course pravastatin treatment o n endothelial function in CAs obtained in control and insulin-resistant rat s with fructose-induced hypertension. Methods. Thirty rats were divided into two experimental groups, in which 14 were fed a regular diet and 16 were fed a fructose-enriched diet for 3 wee ks. The rats were then divided into four groups: control, pravastatin-treat ed control, fructose-fed, and pravastatin-treated fructose-fed. Pravastatin was administered (20 mg/kg/day) for 2 weeks. Excretion of the urinary nitr ic oxide (NO) metabolite nitrite (NO2-) was also assayed. The CAs from all rats were subsequently removed and assessed for endothelium-dependent and - independent vascular reactivity in vitro. The rats in the fructose-fed grou p were insulin resistant, hyperinsulinemic, and hypertensive relative to th e rats in the control and pravastatin-treated control groups and exhibited diminished endothelium-dependent vasomotion and urinary NO2- excretion (p < 0.05), with preserved endothelium-independent vasomotion. Strikingly, prav astatin treatment restored endothelium-dependent vasomotion and urinary NO2 - excretion in rats in the fructose-fed pravastatin-treated relative to the fructose-fed group (p < 0.05). Conclusions. The authors report, for the first time, that pravastatin resto res endothelial function in CAs from insulin-resistant rats with fructose-i nduced hypertension. These beneficial effects were ascribed to direct, chol esterol-independent vascular effects of pravastatin and are likely the resu lt of augmentation of NO production. These data provide impetus for further investigation of nonlipid-lowering indications for pravastatin therapy in the prevention and treatment of CA disease.