Effects of smoking and nicotine on human prostacyclin and thromboxane production in vivo and in vitro.

We studied the effects of smoking and nicotine on the production of proaggregatory thromboxane A2 (TxA2), antiaggregatory prostacyclin (epoprostenol, PGI2), and on lipid peroxidation in vivo and in vitro. In the in vivo study, serum concentrations of thromboxane B2 (TxB2), a stable metabolite of TxA2, increased immediately after smoking three cigarettes but not after smoking the equivalent amount of tobacco in a pipe, whereas serum lipid peroxide values did not change in either group. In vitro, nicotine (2 X 10(-3) mol/liter) inhibited pulmonary TxB2 production by 70% and simultaneously stimulated the production of 6-keto-prostaglandin F1 alpha, a stable metabolite of PGI2, by 40%, which suggest that nicotine does not exert its effect at the cyclooxygenase level. During aggregation in platelet-rich plasma, TxB2 production was inhibited by 53% with 2 X 10(-3) mol/liter of nicotine, and during whole blood clotting the inhibition was 34% with 2 X 10(-4) mol/liter of nicotine. Thus the rise in cigarette smokers' serum TxB2 was probably caused by some constituent of cigarette smoke other than nicotine. The increased production of TxA2 following cigarette smoking may provide one explanation for the increased incidence of atherosclerosis and its complications in cigarette smokers.