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 arachidonic acid metabolism in vivo. In six healthy, non-smoking males, platelet aggregability was assessed by filtragometry and impedance aggregometry before, during and after an intravenous infusion of nicotine at two different doses (0.25 and 0.5 microgram kg-1 min-1) for 30 min. The aggregatory response was also measured after the addition of nicotine at final concentrations ranging from 10(-11) mol L-1 directly to the aggregating blood. The synthesis of thromboxane A2 (TxA2) in platelets was estimated by quantitating the urinary excretion of 2.3-dinor-thromboxane B2 (Tx-M). Despite the plasma concentrations of nicotine, cotinine and catecholamines in the range of those occurring during acute cigarette exposure, the excretion of Tx-M (204 +/- 36 pg mg-1 creatinine) remained unaltered during nicotine infusion. Similarly, platelet aggregatory response to collagen was not influenced by nicotine when infused or added in vitro. However, an enhanced aggregability was detected by filtragometry during the infusion of nicotine at the higher dose employed. The results indicate that nicotine, infused at moderate doses, produces a weak platelet stimulation that is not accompanied by significant release of thromboxane A2, as monitored by urinary excretion of Tx-M. Although a direct action of nicotine on platelets cannot be excluded, it appears more likely that the enhancement of platelet function is mediated by other, secondary mechanisms.
Nowak
J
J
Department of Clinical Physiology, Karolinska Institute at Huddinge University Hospital, Sweden.
Andersson
K
K
Benthin
G
G
Chen
J
J
Karlberg
K E
KE
Sylvén
C
C
D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002395:Catecholamines / Q000097:blood; D003094:Collagen / Q000494:pharmacology; D003367:Cotinine / Q000097:blood; D004573:Electrolytes / Q000097:blood; D006801:Humans; D008297:Male; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D013931:Thromboxanes / Q000652:urine*; D014554:Urination / Q000187:drug effects*
D002395:Catecholamines; D004573:Electrolytes; D013931:Thromboxanes; D016718:Arachidonic Acid; D009538:Nicotine; D003094:Collagen; D003367:Cotinine