Long-term smoking causes nitroglycerin resistance in platelets by depletion of intraplatelet glutathione

Citation
N. Haramaki et al., Long-term smoking causes nitroglycerin resistance in platelets by depletion of intraplatelet glutathione, ART THROM V, 21(11), 2001, pp. 1852-1856
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
1079-5642 → ACNP
Volume
21
Issue
11
Year of publication
2001
Pages
1852 - 1856
Database
ISI
SICI code
1079-5642(200111)21:11<1852:LSCNRI>2.0.ZU;2-B
Abstract
We investigated whether platelet responsiveness to nitroglycerin (NTG) is m aintained in long-term smokers and if not, the mechanism. In the absence or presence of NTG, intraplatelet reduced glutathione (GSH) levels and ADP-in duced platelet aggregation and intraplatelet cGMP levels were measured in 1 0 long-term smokers and 10 age-matched nonsmokers. The intraplatelet GSH le vel was significantly lower in smokers than in nonsmokers (P < 0.05). Plate let aggregation was dose-dependently inhibited by NTG in both groups; howev er, inhibition was significantly weaker in smokers. N-acetylcysteine (1 mmo l/L), an exogenous thiol agent, significantly potentiated NTG-induced plate let inhibition in nonsmokers but not in smokers. The ADP-induced intraplate let cGMP level was significantly greater in the presence of NTG in nonsmoke rs but not so in smokers. Because the effects of long-term smoking are mult ifactorial, a rabbit model was made by chronic administration of buthionine sulfoximine (BSO, n = 6) to decrease intraplatelet GSH. The intraplatelet GSH level was significantly lower in BSO-treated rabbits than in saline-tre ated rabbits (P < 0.001). The NTG-induced inhibition of platelet aggregatio n was significantly weaker in BSO rabbits. N-acetylcysteine-induced potenti ation was not observed in BSO rabbits, whereas significant potentiation was found in saline rabbits. These findings were similar to those of long-term smokers. In contrast, the intraplatelet GSH-to-oxidized glutathione ratio; which represents the redox state of glutathione, was significantly lower i n smokers than in nonsmokers, whereas no difference was found between salin e rabbits and BSO rabbits. In conclusion, long-term smoking causes NTG resi stance to aggregation in platelets, possibly through the depletion of intra platelet GSH.