Pa. Whiss et al., Acute effects of nicotine infusion on platelets in nicotine users with normal and impaired renal function, TOX APPL PH, 163(2), 2000, pp. 95-104
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.