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Acute Effects of Nicotine Infusion on Platelets in Nicotine Users with Normal and Impaired Renal Function
Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0003-3184-0427
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
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2000 (English)In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 163, no 2, 95-104 p.Article in journal (Refereed) Published
Abstract [en]

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 (β-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.

Place, publisher, year, edition, pages
2000. Vol. 163, no 2, 95-104 p.
Keyword [en]
Nicotine, cotinine, platelets, P-selectin, nitric oxide, healthy subjects, renal failure
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-25232DOI: 10.1006/taap.1999.8853Local ID: 9671OAI: diva2:245559
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2013-09-03Bibliographically approved
In thesis
1. Platelet adhesion and P-selectin surface expression
Open this publication in new window or tab >>Platelet adhesion and P-selectin surface expression
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Upon injury in a blood vessel, platelets become activated and adbere to prevent blood loss. Activated platelets express adhesion molecules on their surface that also make leukocytes adhere to the injury. One such molecule, which also is expressed on endothelium, is the glycoprotein P-selectin. The present studies were focused on how soluble factors and surfaces can affect P-selectin surface expression on human platelets.

This thesis presents an enzyme-linked immunosorbent assay (ELISA) application to study platelet expression and release of P-selectin. The well-known platelet activators collagen, epinephrine, ADP, ristocetin, PMA, and thrombin induced surface expression of P-selectin with different potency and time-dependency in vitro. One of the most powerful platelet activators, thrombin, rapidly mediated both surface expression and release. The surface expression decreased after a short peak upon maximal thrombin-activation. The protein kinase C activator PMA induced surface expression equivalently to thrombin but the release of Pselectin was less as compared to thrombin. Nitric oxide (NO) donors, which mimic a vessel wall mechanism to inhibit platelet activation, decreased expression and release of P-selectin upon activation. Adenosine, another agent that is produced in vivo, acted in concert with NO and totally inhibited P-selectin expression induced by thrombin. NO and adenosine act by increasing the second messengers cGMP and cAMP, respectively.

The effects of an infusion of nicotine on platelet P-selectin expression were studied in nicotine users with normal and impaired renal function. After a peak directly after infusion, the plasma concentration of nicotine declined towards the basal level and the level of NO-products was lower as compared to baseline 2 h after infusion. At the same time, P-selectin expression induced by weak activators, but not by thrombin, increased in both groups. A transient and weak inhibition of collagen-induced platelet aggregation was observed directly after infusion. Studies in vitro showed that nicotine per se inhibits P-selectin expression. Thus, nicotine appears to initially inhibit and then increase platelet activation in vivo.

The adhesion of platelets to surfaces that can be exposed upon vessel wall injury and the subsequent expression of P-selectin were found to be dependent on divalent cations. Mg2+ dose-dependently increased platelet adhesion to both collagen and fibrinogen in the physiological range, but supraphysiological concentrations decreased the adhesion to fibrinogen. Ca2+ did only increase platelet adhesion to fibrinogen. Platelet adhesion to collagen caused more expression of P-selectin than adhesion to fibrinogen. Thus, the surface and the access of divalent cations regulate platelet adhesion and P-selectin surface expression.

In summary, multiple factors rep1late and affect platelet adhesion and P-selectin surface expression. The methods presented in this thesis are suitable for studies to further understand and make pharmacological modulation possible of these complex mechanisms and consequences.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 86 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 641
divalent cations, ELISA, nicotine, nitric oxide, platelet adhesion, P-selectin
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-27555 (URN)12216 (Local ID)91-7219-742-0 (ISBN)12216 (Archive number)12216 (OAI)
Public defence
2000-10-06, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-09-03Bibliographically approved

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Whiss, Per A.Bengtsson, TorbjörnLindahl, Tomas
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