Preservation of Endothelium-Dependent and Nω-Nitro-L-Arginine Methyl Ester- and Indomethacin-Resistant Arterial Relaxation in High-Cholesterol-Diet Fed Rabbits by Treatment with Fluvastatin, an HMG-CoA Reductase Inhibitor

This study was designed to test the hypothesis that fluvastatin preserves endothelium-dependent and nitric oxide (NO)-independent relaxations in arterial preparations from rabbits fed a high-cholesterol diet in the absence of any cholesterol-lowering action. Rabbits were fed a 0.5% high-cholesterol diet for 12 weeks and then fed the high-cholesterol diet with/without fluvastatin 2 mg/kg/d for an additional 8 weeks. Plasma total and LDL-cholesterol concentrations were not affected by fluvastatin treatment. Endothelium-dependent and NO-mediated relaxation elicited by acetylcholine and A23187 in both the thoracic aorta and femoral artery was impaired in the high-cholesterol group but not in the fluvastatin-treated group. Endothelium-independent relaxation elicited by sodium nitroprusside was similar among the 3 groups. Preincubation of thoracic aortas from each of the 3 groups with Nω-nitro-L-arginine methyl ester (l-NAME) and indomethacin completely abolished the relaxant response to acetylcholine. In contrast, the maximal response to acetylcholine (1 μM) in femoral artery was only partially reversed in the presence of l-NAME and indomethacin. Fluvastatin treatment preserved the acetylcholine- induced l-NAME and indomethacin-resistant relaxation impaired in the femoral artery from the high-cholesterol diet group. These results suggest that fluvastatin treatment preserves endothelium- dependent, NO-independent function as well as NO-dependent function in absence of its lipid lowering-action.