Long-term Smoking Impairs Platelet-Derived Nitric Oxide Release

Abstract

Background Long-term smoking impairs endothelium-dependent vasodilation, which is mediated by nitric oxide (NO). However, it is unknown whether long-term smoking impairs the platelet-derived NO release, which regulates platelet aggregation. Methods and Results Platelet-derived electrical current induced by collagen was measured with an NO-selective electrode in 12 smokers and 11 nonsmokers. Collagen-induced intraplatelet cGMP and platelet aggregation was measured in smokers and nonsmokers. S -nitroso- N -acetyl- dl -penicillamine, a direct NO donor, dose dependently increased in electrical current ( r =.99). Collagen induced platelet aggregation and dose dependently increased electrical current ( r =.94). Collagen-induced electrical current and cGMP were significantly augmented by l -arginine, a precursor of NO, and attenuated by N G -monomethyl- l -arginine, an inhibitor of NO synthesis. Significant correlation was found between collagen-induced electrical current and cGMP ( r =.73). These findings indicate that the change in electrical current reflects the NO release through the l -arginine–NO pathway in platelets. Collagen-induced electrical current (6.7 versus 13.8 pA; P <.001) and cGMP (1.2 versus 3.0 pmol/10 9 platelets; P <.005) were significantly lower in smokers than in nonsmokers. Although l -arginine increased cGMP levels in both smokers and nonsmokers, the level was still lower in smokers than in nonsmokers. The inhibitory effect of l -arginine on collagen-induced platelet aggregation was significantly lower in smokers than in nonsmokers ( P <.05). Conclusions These findings provide evidence that platelet-derived NO release is significantly impaired in long-term smokers, resulting in the augmentation of platelet aggregability.