Acute effects of nicotine infusion on platelets in nicotine users with normal and impaired renal function

The role of platelets in cardiovascular disease associated with smoking is becoming more established, but the effects of nicotine on platelets are unc lear. Nicotine therapy is used for smoking cessation in both health and dis ease. Consequently, the effects of nicotine on platelets are of particular significance in disorders such as renal disease, which is associated with d efective platelet function, increased cardiovascular morbidity, and altered nicotine metabolism. Thus, the aim of the present study was to investigate the acute effects of nicotine infusion (NI) on platelets in seven healthy subjects (HS) and seven patients with renal failure (RF). All subjects were nicotine users and had refrained from using nicotine for 36 h before NI. B lood was collected before, immediately after, and 2 h after NI. The plasma concentrations of nicotine and its main metabolite cotinine were determined by gas chromatography. Platelet responsiveness was assessed by aggregometr y and flow cytometry in whole blood (P-selectin surface expression, fibrino gen- and von Willebrand factor-binding), P-selectin expression in isolated platelets, and immunoassays of platelet release (beta-thromboglobulin, plat elet factor 4, and soluble P-selectin) and nitric oxide (NO) products. The plasma levels of cotinine, but not nicotine, were significantly higher in R F compared to HS at all time points. In both groups, collagen-induced plate let aggregation was restrained immediately after NI, when the plasma concen tration of nicotine was maximal, and was restored after 2 h. Two hours afte r NI, activation-dependent P-selectin surface expression in isolated platel ets increased in both groups. This increased platelet responsiveness occurr ed simultaneously with a significant increase of plasma cotinine and a decr ease of NO products. Thus, the present study suggests that nicotine, direct ly or through some secondary mechanism or metabolite, only slightly potenti ates some of the platelet responses. Renal failure appears not to influence the effects of nicotine on platelets. (C) 2000 Academic Press.