Short-term effects of transdermal nicotine on acute tissue plasminogen activator release in vivo in man.
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.
Pellegrini
M P
MP
Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Crewe Road, EH4 2XU, Edinburgh, Scotland, UK.
Newby
D E
DE
Maxwell
S
S
Webb
D J
DJ
D000279:Administration, Cutaneous; D000328:Adult; D000941:Antigens / Q000097:blood; D001916:Brachial Artery / Q000187:drug effects; D003367:Cotinine / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D009599:Nitroprusside; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000276:immunology / Q000378:metabolism*; D014665:Vasodilator Agents
D000941:Antigens; D014665:Vasodilator Agents; D009599:Nitroprusside; D013373:Substance P; D009538:Nicotine; D010959:Tissue Plasminogen Activator; D003367:Cotinine