Biochemical evidence of a chronic abnormality in platelet and vascular function in healthy individuals who smoke cigarettes.
Cigarette smoking is associated with increased mortality from cardiovascular disease that declines after cessation. This study extends the evidence regarding the effects of chronic smoking on platelets and the vessel wall in vivo. Excretion of a major urinary thromboxane metabolite, 2,3-dinor-thromboxane B2, is significantly (p less than .01) elevated in apparently healthy chronic smokers (20 cigarettes daily) compared with that in nonsmoking control subjects. This difference in excretion of 2,3-dinor-thromboxane B2 was abolished by the administration of 20 mg aspirin twice daily, a dose shown to selectively inhibit platelet cyclooxygenase. After aspirin, the return of the excretion of 2,3-dinor-thromboxane B2 to pretreatment levels paralleled the recovery of platelet cyclooxygenase. These findings indicate that excessive thromboxane A2 generation in chronic smokers predominantly derives from platelets. The urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha also is increased during chronic cigarette smoking, as is the case with other diseases associated with accelerated interaction of platelets with the vessel wall. We have found evidence of platelet and vascular dysfunction in vivo in chronic cigarette smokers before the manifestation of overt cardiovascular disease. The results would also be consistent with the hypothesis that in chronic smokers, the platelet defect is largely reflective of smoking-induced vascular injury.
Nowak
J
J
Murray
J J
JJ
Oates
J A
JA
FitzGerald
G A
GA
D000328:Adult; D001791:Blood Platelet Disorders / Q000209:etiology*; D001792:Blood Platelets / Q000378:metabolism; D003367:Cotinine / Q000097:blood; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000097:blood; D010974:Platelet Aggregation; D012907:Smoking; D013929:Thromboxane B2 / Q000097:blood; D013931:Thromboxanes / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology*
D013931:Thromboxanes; D013929:Thromboxane B2; D009538:Nicotine; D011464:Epoprostenol; D003367:Cotinine