Short-term effects of transdermal nicotine on acute tissue plasminogen activator release in vivo in man

M P Pellegrini, D E Newby, S Maxwell, D J Webb

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: Cigarette smoking impairs peripheral endothelium-dependent vasodilatation and acute tissue plasminogen activator (t-PA) release in man. The aim of the study was to determine if this endothelial dysfunction is, in part, mediated by the effects of nicotine.

METHODS: Blood flow and plasma fibrinolytic factors were measured in both forearms of eight healthy male non-smokers during unilateral brachial artery infusion of the endothelium-dependent vasodilator, substance P (2 to 8 pmol/min). Endothelium-independent vasodilatation was assessed using intra-arterial infusion of sodium nitroprusside (2 to 8 microg/min). Subjects attended after 7 days treatment with transdermal nicotine or placebo in a double blind randomised crossover design.

RESULTS: Plasma cotinine concentrations rose from 0.4+/-0.1 (placebo) to 125+/-25 ng/ml during nicotine administration (P<0.001). On both treatment days, substance P caused dose-dependent increases in blood flow and plasma t-PA antigen and activity concentrations (P<0.001 for all) but had no effect on plasma plasminogen activator inhibitor type 1 (PAI-1) concentrations. Compared with placebo, nicotine administration increased the substance-P-induced release of t-PA antigen and activity (P<0.05 for both) without an effect on endothelium-dependent or -independent vasodilatation.

CONCLUSIONS: Short-term transdermal nicotine treatment does not affect endothelium-dependent vasomotion but does increase substance-P-induced t-PA release in vivo in man. This suggests that nicotine administration alters specific aspects of endothelial function and enhances the acute endogenous fibrinolytic capacity in vivo. The long-term effects of nicotine exposure, including the potential to cause depletion of endothelial t-PA stores, now needs to be assessed.

Original languageEnglish
Pages (from-to)321-7
Number of pages7
JournalCardiovascular Research
Issue number2
Publication statusPublished - 1 Nov 2001


  • Administration, Cutaneous
  • Adult
  • Antigens
  • Brachial Artery
  • Cotinine
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endothelium, Vascular
  • Fibrinolysis
  • Humans
  • Male
  • Nicotine
  • Nitroprusside
  • Plethysmography
  • Regional Blood Flow
  • Substance P
  • Time Factors
  • Tissue Plasminogen Activator
  • Vasodilator Agents


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