A Decreased Responsiveness of Platelet to Nitric Oxide in Cholesterol-Fed Rabbits

Objective:To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to induce atherosclerosis.Serum NOx levels and the responsiveness of platelet to NO donor SNP were determined every 4 weeks during maintaining on a chow containing 1% cholesterol.The measurement of serum lipids and the examination of morphological feature and endothelial-dependent relaxation of aorta were performed after 12 weeks of cholesterol diet. Results:Cholesterol diet significantly increased serum levels of cholesterol and LDL,caused a remarkable platelet hyperaggregability,and produced an evident endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine and endothelial cell lesion as exhibited by scanning electron microscope examination.The percentage of inhibition of ADP-induced platelet aggregation by NO donor SNP was significantly smaller in cholesterol chow group than that in normal chow group although no significant difference in serum NOx levels between normal and cholesterol chow group was observed throughout the development of atherosclerosis. Conclusion:The present study suggests that the endothelial dysfunction caused by enhanced serum cholesterol and LDL levels induces a decreased responsiveness of platelet to NO.