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.


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 NG-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.
Ichiki
K
K
Third Department of Internal Medicine, Kurume University School of Medicine, Japan.
Ikeda
H
H
Haramaki
N
N
Ueno
T
T
Imaizumi
T
T
D000328:Adult; D001120:Arginine / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D006152:Cyclic GMP / Q000097:blood; D004553:Electric Conductivity; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009569:Nitric Oxide / Q000097:blood*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D012016:Reference Values; D012044:Regression Analysis; D026423:S-Nitroso-N-Acetylpenicillamine; D012907:Smoking / Q000097:blood*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D003094:Collagen; D001120:Arginine; D010396:Penicillamine; D006152:Cyclic GMP