Antioxidative action of aspirin on endothelial function in hypercholesterolaemic rats.

The role of aspirin on vascular endothelial changes during hypercholesterolaemia prior to development of actual atherosclerotic lesions is not known. Therefore, in the present study, we tested the hypothesis that aspirin by its antioxidant action improves endothelial function in a rat model of hypercholesterolaemia. Hypercholesterolaemia was induced in Wistar rats by feeding a 1% cholesterol-rich diet for 10 weeks. Lipid profile, lipid peroxidation and reduced glutathione were estimated in serum. Endothelial function and beta(2)-adrenoceptor activity was tested by studying the dose-response relationship of acetylcholine and isoproterenol, respectively, on isolated aortic tissues in an organ bath setup. Hypercholesterolaemic rats showed a significant increase in total cholesterol, low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C), and a significant fall in high-density lipoprotein cholesterol (HDL-C) compared to the control rats. Isolated aortic tissues from hypercholesterolaemic rats showed endothelial dysfunction and decreased sensitivity to beta(2)-adrenoceptor. Treatment with aspirin was associated with a fall in total cholesterol, LDL-C and VLDL-C, and a significant rise in serum HDL-C. Aspirin treatment also restored endothelial function and beta(2)-adrenoceptor activity. Hypercholesterolaemic rats showed free radical generation, evident by increase in serum lipid peroxidation and reduction in serum reduced glutathione content compared to the control rats. Aspirin treatment was associated with reduction in free radical stress evident by decreased lipid peroxidation and significantly prevented reduction in glutathione content compared to hypercholesterolaemic controls. Aspirin improves endothelial function and beta(2)-adrenoceptor activity during experimentally induced hypercholesterolaemia in rats, possibly due to an antioxidant effect.