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CLINICAL STUDY

Augmented oxidative stress of platelets in chronic smokers

Mechanisms of impaired platelet-derived nitric oxide bioactivity and augmented platelet aggregability

^a Department of Internal Medicine III and Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan

Manuscript received October 18, 2000; revised manuscript received June 18, 2001, accepted July 12, 2001.

^* Reprint requests and correspondence: Dr. Hisao Ikeda, Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
ikeikeda{at}med.kurume-u.ac.jp

OBJECTIVES

We investigated whether impaired platelet-derived nitric oxide (PDNO) bioactivity and augmented platelet aggregability in chronic smokers are related to the imbalance of the intraplatelet redox state through increased oxidative stress.

BACKGROUND

Chronic smoking impairs PDNO release and augments platelet aggregability. However, their mechanisms are unknown.

METHODS

Collagen-induced PDNO release, platelet aggregation, plasma and intraplatelet vitamin C and reduced glutathione (GSH), intraplatelet cyclic guanosine 3',5'-monophosphate (cGMP) and intraplatelet nitrotyrosine production, which is a marker of the peroxynitrite formation, were measured in 11 chronic smokers and 10 age-matched nonsmokers.

RESULTS

Release of PDNO and levels of intraplatelet cGMP were lower, and platelet aggregation was greater, in smokers than in nonsmokers. Intraplatelet vitamin C and GSH levels were lower in smokers than in nonsmokers. Intraplatelet nitrotyrosine production was greater in smokers than in nonsmokers. Next, we investigated the effects of oral vitamin C administration (2 g). After vitamin C administration, intraplatelet vitamin C levels were increased and not different at 2 h between the two groups. Then, PDNO release, intraplatelet cGMP levels and platelet aggregation in smokers were restored to the levels of nonsmokers. In smokers, PDNO release and consumption of GSH during platelet aggregation were inversely correlated, and consumption was much less after vitamin C administration. Vitamin C administration decreased intraplatelet nitrotyrosine production in smokers.

CONCLUSIONS

Impaired PDNO bioactivity and augmented platelet aggregability may be caused by an imbalance of the intraplatelet redox state through increased oxidative stress in smokers.

Abbreviations and Acronyms   cGMP = cyclic guanosine 3',5'-monophosphate   GSH = reduced glutathione   IgG = immunoglobulin G   L-NAME = NG-nitro-L-arginine methylester   L-NMMA = NG-monomethyl-L-arginine   NO = nitric oxide   NOS = nitric oxide synthase   PDNO = platelet-derived nitric oxide

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