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Abstract

Aliskiren Protects against Hypercholesterolemia and Oxidative Stress on Isolated Aortae in Cholesterol-Fed Rats

Sahar Mohamed Kamal

Background: Atherosclerosis and endothelial dysfunction are important associated disorders in the majority of hypertensive patients. Many studies are directed towards investigating any possible anti-hyperlipidemic effect with improvement of arterial compliance of newer generations of antihypertensive drugs so as to reduce the number of drugs used to treat those patients.
Aim: The present study aims to determine the effects of aliskiren, a direct renin inhibitor, on serum cholesterol and some anti-oxidant enzymes together with aortic TBARS and vasorelaxant effect of acetyl-choline (Ach) on isolated aortic rings of cholesterol-fed rats.
Methods: The duration of the study was 12 weeks. Twenty-four rats were randomly divided into 3 groups (n=8 rats/group). Group (1) is control, received 0.5% carboxymethylcellulose (CMC) sodium, as a solvent of aliskiren, and fed ordinary diet. Group (2) fed 2% (w/w) cholesterol diet + CMC sodium. Group (3) was fed with 2% (w/w) cholesterol diet with ip daily administration of aliskiren at a dose of 5 mg/kg for 12 weeks. Systolic blood pressure (SBP) was assessed both at the beginning and at the end of every 4 weeks of the study. Serum total cholesterol, superoxide dismutase (SOD) enzyme in erythrocyte lysates, thiobarbituric acid reactive substance [TBARS] content, activities of catalase and glutathione enzymes in aortic homogenates of tested rats were measured. The thoracic aortae were removed from all tested rats to assess the vasorelaxant effect of Ach.
Results: Aliskiren-treated group (3) showed a significant improvement of all the markers in comparison with nontreated cholesterol-fed rats. SBP of treated group was maintained at levels comparable to control group (1) with marked improvement in aortic reactivity to ACh compared to group (2).
Conclusion: Aliskiren could possess an anti-hypercholestrolemic and an ability to improve aortic reactivity via an anti-oxidant effect and a reduction in lipid peroxidation in cholesterol-fed rats.