Nicotine impairs endothelium-dependent dilatation in human veins in vivo.
BACKGROUND
Cigarette smoking is associated with impaired endothelium-dependent dilatation in human veins and arteries. An in vivo study in animals suggests that nicotine may contribute to this abnormality. We tested the hypothesis that local administration of nicotine at a dose reproducing the plasma concentration observed during smoking would impair endothelium-dependent vasodilatation in human veins in vivo.


METHODS
We studied 11 healthy nonsmokers with the dorsal hand vein compliance technique. After 70% to 80% preconstriction with phenylephrine, endothelium-dependent venous relaxation was assessed by infusion of bradykinin (1 to 278 ng/min), a potent vasodilator acting primarily in this model through endothelial release of nitric oxide and prostanoids. Sodium nitroprusside (0.0001 to 3166 ng/min) was used to test endothelium-independent relaxation. Dose-response curves were constructed before and during nicotine coinfusion at a rate of 40 ng/min, reproducing a plasma concentration of 15 ng/mL.


RESULTS
After a 10-minute preinfusion, nicotine administration was associated with a loss in sensitivity to bradykinin (P < .001). After 30 and 60 minutes of preinfusion with nicotine, the venorelaxant effect of bradykinin was further reduced (P < .001). A similar inhibition of the response to bradykinin by nicotine persisted in the presence of indomethacin (INN, indomethacin). Coinfusion of nicotine did not attenuate sodium nitroprusside-induced venodiiation.


CONCLUSIONS
The results show that acute local exposure to nicotine in vivo is associated with an impaired response to endothelium-derived nitric oxide in human veins. This finding may provide further insight into the pathophysiology of smoking-induced endothelial dysfunction.
Chalon
S
S
Department of Medicine, Stanford University School of Medicine, Calif., USA.
Moreno
H
H
Benowitz
N L
NL
Hoffman
B B
BB
Blaschke
T F
TF
D000328:Adult; D000704:Analysis of Variance; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D015203:Reproducibility of Results; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects
D018722:Nicotinic Agonists; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009538:Nicotine; D001920:Bradykinin