Distinct effects of acute and chronic nicotine application on microvascular thrombus formation and endothelial function in male and female mice.
OBJECTIVE
Cigarette smoking is linked to thromboembolic events; however, a relationship between nicotine exposition and thrombosis has not been established. Thus, we intended to study the effect of acute and chronic nicotine application in an in vivo mouse model.


METHODS
In microvessels of the dorsal skin fold chamber, light-dye-induced thrombus formation was analyzed using intravital fluorescence microscopy. Male and female C57BL/6J mice received nicotine chronically via the drinking water (100 microg/ml) for 8 weeks. An additional series of experiments was performed with acute iv nicotine treatment (3 mg/kg body weight).


RESULTS
No significant differences in microvascular thrombus formation were detected after chronic nicotine application in male and female animals when compared with controls. Accordingly, flow cytometric analysis did not show significant effects on platelet activity. Chronic nicotine treatment resulted in a significantly reduced endothelial activation in male, but not in female mice. In contrast, acute iv application of nicotine revealed significantly shorter thrombosis times in arterioles of female mice and a significantly increased endothelial P-selectin expression in mice of both genders.


CONCLUSIONS
Chronic nicotine application does not promote microvascular thrombus formation in mice of either gender, whereas acute high-dose iv administration caused a significant increase of arteriolar thrombosis in female animals probably via a synergistic effect of increased endothelial P-selectin expression and female hormone levels. A gender-dependency of acute nicotine action can be presumed.
Lindenblatt
Nicole
N
Institute for Experimental Surgery, University of Rostock, Schillingallee 70, 18055 Rostock, Germany. niclindenblatt@hotmail.com
Platz
Uwe
U
Hameister
Jörn
J
Klar
Ernst
E
Menger
Michael D
MD
Vollmar
Brigitte
B
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003367:Cotinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D019007:P-Selectin / Q000097:blood; D012737:Sex Factors; D013927:Thrombosis / Q000139:chemically induced* / Q000378:metabolism; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014699:Venules / Q000187:drug effects / Q000378:metabolism
D018722:Nicotinic Agonists; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009538:Nicotine; D003367:Cotinine