Long-term smoking impairs platelet-derived nitric oxide release

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.