Platelet-derived nitric oxide and coronary risk factors

Platelet aggregation is inhibited through a negative feedback mechanism by the L-arginine/nitric oxide (NO) pathway found in platelets themselves. We have shown that long-term smoking impairs the bioactivity of platelet-deriv ed NO (PDNO), resulting in an increased platelet aggregability. However, li ttle is known about the relation between other coronary risk factors and PD NO release. Accordingly, this study was undertaken to examine whether other coronary risk factors are related to the impairment of PDNO bioactivity. W e measured collagen-induced PDNO release with an NO-selective electrode in 61 subjects (mean age 47 years, range 24 to 74 years) who underwent complet e physical and laboratory examinations. There was a significant inverse cor relation between PDNO release and the number of coronary risk factors (r = -0.61, P<0.001). Univariate analysis showed a significant inverse correlati on between PDNO release and age (r = -0.33, P<0.01), mean arterial pressure (r = -0.40, P<0.002), total cholesterol level (r = -0.31, P<0.02), and LDL -cholesterol level (r = -0.33, P<0.02). PDNO release was significantly lowe r in long-term smokers than in nonsmokers (P<0.001). With multiple stepwise regression analysis. PDNO release correlated significantly and independent ly (r = 0.51), with smoking (F = 37.8), age (F = 7.1), and mean arterial pr essure (F = 5.1). Thus, we demonstrated that coronary risk factors are asso ciated with an impairment of PDNO release by human platelets. Our findings may contribute to the understanding of the pathophysiological link between coronary risk factors and atherothrombotic disease.