EFFECT OF NICOTINE INFUSION IN HUMANS ON PLATELET-AGGREGATION AND URINARY-EXCRETION OF A MAJOR THROMBOXANE METABOLITE

The objective of this study was to evaluate further a possible role of nicotine as a stimulator of platelet aggregability and platelet arach idonic acid metabolism in vivo. In six healthy. non-smoking males. pla telet aggregability was assessed by filtragometry and impedance aggreg ometry before, during and after an intravenous infusion of nicotine at two different doses (0.25 and 0.5 mu g kg(-1) min(-1)) for 30 min. Th e aggregatory response was also measured after the addition of nicotin e at final concentrations ranging from 10(-11) mol L(-1) to 10(-5) mol L(-1) directly to the aggregating blood. The synthesis of thromboxane A(2) (TxA(2)) in platelets was estimated by quantitating the urinary excretion of 2.3-dinor-thromboxane B-2 (Tx-M). Despite the plasma conc entrations of nicotine, cotinine and catecholamines in the range of th ose occurring during acute cigarette exposure. the excretion of Tx-M ( 204+/-36 pg mg(-1) creatinine) remained unaltered during nicotine infu sion. Similarly. platelet aggregatory response to collagen was not inf luenced by nicotine when infused or added in vitro. However, an enhanc ed aggregability was detected by filtragometry during the infusion of nicotine at the higher dose employed. The results indicate that nicoti ne, infused at moderate doses, produces a weak platelet stimulation th at is not accompanied by significant release of thromboxane A(2), as m onitored by urinary excretion of Tx-M. Although a direct action of nic otine on platelets cannot be excluded, it appears more likely that the enhancement of platelet function is mediated by other, secondary mech anisms.