Nitric oxide-dependent inhibition of platelet aggregation in elderly patients with hypercholesterolemia

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 240 mg/dl or more (n = 21). In elderly controls with Tchol less than 240 mg/dl (n = 61), L-arginine (5-50 mM) inhibited ADP-induced platelet aggregation in a dose-dependent manner (42.4% inhibition at 50 mM). 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 12.5-50 uM 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 160 mg/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.