Excretion of thromboxane metabolites in healthy women after cessation of smoking.

Abstract

Cigarette smokers, but not former smokers, excrete more thromboxane A 2 (TxA 2 ) metabolites in the urine than do lifelong nonsmokers, which suggests chronic activation of their platelets. To further characterize the effect elicited by smoking on platelet function, we followed the change in urinary excretion of the 2,3-dinor (Tx-M) and 11-dehydro (dTx) metabolites of TxAj, analyzed by gas chromatography/mass spectrometry and radioimmunoassay, respectively, in eight healthy women who quit habitual smoking and compared it with the recovery of these metabolites after a single dose of acetylsalicylic acid (ASA). Tx-M and dTx before cessation of smoking were approximately 550 and 600 pg/mg creatinine, respectively. Within 3 days after quitting smoking, Tx-M and dTx had dropped to stable levels of approximately 300 and 350 pg/mg, respectively. The rates of change in excretion of Tx-M and dTx after smoking cessation were more rapid (p<0.02 and 0.02, respectively) than those observed during the recovery of platelet function after a single dose of ASA. The excretion of 2,3-dinor-6-keto-prostaglandin ¥ l a , a metabolite of prostacyclin, was not affected by smoking cessation. We conclude that cigarette smoking elicits an increase in platelet activity in the absence of vascular injury. This increase is reversible within the life span of the platelets. {Arteriosclerosis and Thrombosis 1993;13:777-782) KEY WORDS • acetylsalicylic acid • cardiovascular risk factors • cigarette smoking • platelets • prostacyclin • thromboxanes • urineC igarette smoking is a major risk factor for cardiovascular disease; the risk increases progressively as daily cigarette consumption increases.1 " 5 After cessation of smoking the risk drops rather rapidly toward the level observed in nonsmokers. 6 -9 Platelets are thought to play an important role in cardiovascular disease, 10 ' 11 but the effect of smoking on platelet function is poorly understood. Smokers have been reported to display biochemical evidence of increased activation of platelets in vivo. "15 These data may indicate facilitation of platelet aggregability as a significant etiologic factor in smoking-associated cardiovascular disease.Thromboxane A 2 (TxA 2 ) is formed in platelets from arachidonic acid.16 TxA 2 has platelet proaggregatory and proadhesive properties and is also a strong vasoconstrictor. The administration of acetylsalicylic acid (ASA) in doses that inhibit cyclooxygenase-dependent formation of TxA 2 in platelets has proven efficient in the primary 17 and secondary 18 prevention of acute myocardial infarction. These data indicate that TxA 2 formed in platelets is etiologically involved in certain acute cardio- Received November 18, 1992; revision accepted February 12, 1993. vascular disorders as well as being a marker for platelet activity.Cigarette smoking is linked to an increased incidence of cardiovascular disease in women.19 " 22 Although women seem to develop cardiovascular disease 10-15 years later than men, 23 it is a leading cause of death among women. ...

Effects of smoking cessation and nicotine substitution on systemic eicosanoid production in man

“…It has been suggested that increased prostacyclin synthesis in smokers is a compensatory mechanism of healthy endothelium for the general vasoconstrictive properties of cigarette smoking (Lassila et al 1988), possibly by a mechanism mediated by some constituent(s) of tobacco smoke. Urinary excretion of 11-dehydro-TXB 2 was increased in smokers, which is in line with previous findings of increased systemic thromboxane synthesis in smokers (Nowak et al 1987;Lassila et al 1988;Wennmalm et al 1991;Rångemark et al 1993). Increased thromboxane synthesis reflects platelet activation (Nowak et al 1987).…”

“…Apparently healthy habitual smokers have increased systemic aggregatory and vasoconstrictory thromboxane (TX) A 2 synthesis measured as urinary excretion of 11-dehydro- (Rångemark et al 1993) and 2,3-dinor-TXB 2 (Nowak et al 1987;Lassila et al 1988;Wennmalm et al 1991). There are only few studies on the effects of smoking on the lipoxygenase pathway in man.…”

“…Smoking cessation has been reported to decrease the excretion of 2,3-dinor-TXB 2 and 11-dehydro-TXB 2 (Rånge-mark et al 1993), but to have no effect on the excretion of 2,3-dinor-6-keto-PGF 1α (Rångemark et al 1993). In a study by Benowitz and co-workers (1993) which compared the effects of smoking, transdermal nicotine, and placebo patch, cigarette smoking but not transdermal nicotine increased the urinary excretion of 11-dehydro-TXB 2 , whereas the excretion of 2,3-dinor-6-keto-PGF 1α was not influenced by any of the treatments.…”

Urinary cotinine as a tobacco-smoke exposure index: a minireview

“…A correlation has been demonstrated between daily cigarette consumption as assessed by urinary cotinine determination and the urinary excretion of thromboxane A2 metabolites [71,95,98] but not with urinary excretion of prostacyclin metabolites. This observation can be explained by in vivo platelet activation [98].…”

Relationship between Biomarkers of Cigarette Smoke Exposure and Biomarkers of Inflammation, Oxidative Stress, and Platelet Activation in Adult Cigarette Smokers

“…The level of 11-dehTxB 2 has been reported to be higher in smokers than in nonsmokers (25). Switching from smoking cigarettes to transdermal nicotine patch (30) or smoking cessation leads to decreased urinary 11-dehTxB 2 excretion (31).…”