Background Long-term smoking impairs endothelium-dependent vasodilatio
n, which is mediated by nitric oxide (NO). However, it is unknown whet
her long-term smoking impairs the platelet-derived NO release, which r
egulates platelet aggregation. Methods and Results Platelet-derived el
ectrical current induced by collagen was measured with an NO-selective
electrode in 12 smokers and 11 nonsmokers. Collagen-induced intraplat
elet cGMP and platelet aggregation was measured in smokers and nonsmok
ers. S-nitroso-N-acetyl-dl-penicillamine, a direct NO donor, dose depe
ndently increased in electrical current (r=.99). Collagen induced plat
elet 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-mono
methyl-L-arginine, an inhibitor of NO synthesis. Significant correlati
on was found between collagen-induced electrical current and cGMP (r=.
73). These findings indicate that the change in electrical current ref
lects the NO release through the L-arginine-NO pathway in platelets. C
ollagen-induced electrical current (6.7 versus 13.8 pA; P<.001) and cG
MP (1.2 versus 3.0 pmol/10(9) platelets; P<.005) were significantly lo
wer in smokers than in nonsmokers. Although L-arginine increased cGMP
levels in both smokers and nonsmokers, the level was still lower in sm
okers than in nonsmokers. The inhibitory effect of L-arginine on colla
gen-induced platelet aggregation was significantly lower in smokers th
an in nonsmokers (P<.05). Conclusions These findings provide evidence
that platelet-derived NO release is significantly impaired in long-ter
m smokers, resulting in the augmentation of platelet aggregability.