title: Acute effects of nicotine infusion on platelets in nicotine users with normal and impaired renal function.
abstract: The role of platelets in cardiovascular disease associated with smoking is becoming more established, but the effects of nicotine on platelets are unclear. Nicotine therapy is used for smoking cessation in both health and disease. Consequently, the effects of nicotine on platelets are of particular significance in disorders such as renal disease, which is associated with defective 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. Blood 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 aggregometry and flow cytometry in whole blood (P-selectin surface expression, fibrinogen- and von Willebrand factor-binding), P-selectin expression in isolated platelets, and immunoassays of platelet release (beta-thromboglobulin, platelet factor 4, and soluble P-selectin) and nitric oxide (NO) products. The plasma levels of cotinine, but not nicotine, were significantly higher in RF compared to HS at all time points. In both groups, collagen-induced platelet aggregation was restrained immediately after NI, when the plasma concentration of nicotine was maximal, and was restored after 2 h. Two hours after NI, activation-dependent P-selectin surface expression in isolated platelets increased in both groups. This increased platelet responsiveness occurred simultaneously with a significant increase of plasma cotinine and a decrease of NO products. Thus, the present study suggests that nicotine, directly or through some secondary mechanism or metabolite, only slightly potentiates some of the platelet responses. Renal failure appears not to influence the effects of nicotine on platelets.
authors.affiliation: Division of Pharmacology, Faculty of Health Sciences, Linköping, SE-581 85, Sweden. Per.Whiss@hul.liu.se
authors.forename: P A
authors.initials: PA
authors.lastname: Whiss
authors.forename: T H
authors.initials: TH
authors.lastname: Lundahl
authors.forename: T
authors.initials: T
authors.lastname: Bengtsson
authors.forename: T L
authors.initials: TL
authors.lastname: Lindahl
authors.forename: E
authors.initials: E
authors.lastname: Lunell
authors.forename: R
authors.initials: R
authors.lastname: Larsson
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003367:Cotinine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D019007:P-Selectin / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000032:analysis; D051437:Renal Insufficiency / Q000097:blood / Q000503:physiopathology*; D012907:Smoking / Q000097:blood; D000074606:Smoking Prevention; D001620:beta-Thromboglobulin / Q000032:analysis; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D019007:P-Selectin; D001620:beta-Thromboglobulin; D014841:von Willebrand Factor; D010978:Platelet Factor 4; D009538:Nicotine; D005340:Fibrinogen; D003367:Cotinine