Abstract
Hypercholesterolemia reduces production of nitric oxide (NO), a potent inhibitor of platelet aggregation, in endothelial cells. Recently platelet has been found to have NO synthase. Hypercholesterolemia may influence platelet NO production. We investigated NO-dependent inhibition of platelet aggregation in elderly hypercholesterolemic patients with total cholesterol (Tchol) of 240mg/dl or more (n=21). In elderly controls with Tchol less than 240mg/dl (n=61), L-arginine (5-50mM) inhibited ADP-induced platelet aggregation in a dose-dependent manner (42.4% inhibition at 50mM). However, L-arginine did not inhibit platelet aggregation in elderly hypercholesterolemic patients. L-arginine increased cyclic GMP production in elderly controls, but not in hypercholesterolemic patients (p<0.02). Hypercholesterolemic patients showed increased platelet aggregation compared with elderly controls (p=0.018). L-nitro-arginine methyl ester 12.5-50uM increased platelet aggregation in both groups. Superoxide dismutase improved L-arginine inhibition of platelet aggregation in elderly hypercholesterolemic patients (p=0.02). LDL cholesterol of 160mg/dl or more was an independent predictor for loss of L-arginine inhibition of platelet aggregation (relative risk 3.9, p=0.0098). This result suggests that hypercholesterolemia causes decreased NO-dependent inhibition of platelet aggregation due to reduced NO utilization. NO-dependent platelet aggregation may be a powerful tool for detection of vascular injury.
