Nicotine impairs endothelium-dependent dilatation in human veins in vivo

Background: Cigarette smoking is associated with impaired endothelium-depen dent dilatation in human veins and arteries. An in vivo study in animals su ggests that nicotine may contribute to this abnormality. We tested the hypo thesis that local administration of nicotine at a dose reproducing the plas ma 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 complia nce technique. After 70% to 80%, preconstriction with phenylephrine, endoth elium-dependent venous relaxation was assessed by infusion of bradykinin (1 to 278 ng/min), a potent vasodilator acting primarily in this model throug h endothelial release of nitric oxide and prostanoids. Sodium nitroprusside (0.0001 to 3166 ng/min) was used to test endothelium-independent relaxatio n, Dose-response curves were constructed before and during nicotine coinfus ion at a rate of 40 ng/min, reproducing a plasma concentration of 15 ng/mL. Results: After a 10-minute preinfusion, nicotine administration was associa ted with a loss in sensitivity to bradykinin (P < .001), After 30 and 60 mi nutes of preinfusion with nicotine, the venorelaxant effect of bradykinin w as further reduced (P < .001), A similar inhibition of the response to brad ykinin by nicotine persisted in the presence of indomethacin (INN, indometa cin), Coinfusion of nicotine did not attenuate sodium nitroprusside-induced venodilation, Conclusion: 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 pathophy siology of smoking-induced endothelial dysfunction.