ENDOTHELIAL DYSFUNCTION IN HUMAN HAND VEINS IS RAPIDLY REVERSIBLE AFTER SMOKING CESSATION

Cigarette smoking has been shown to impair endothelium-dependent dilat ion in arteries. We tested the hypothesis that cigarette smoking also impairs endothelium-dependent venodilation and evaluated changes in th is response after smoking cessation in a time-course study using the d orsal hand vein technique. Dose-response curves were constructed in sm okers and nonsmokers by infusing bradykinin (1-278 ng/min), an endothe lium-dependent vasodilator, and nitroglycerin (0.006-1,583 ng/min), an endothelium-independent vasodilator, into hand veins preconstricted w ith the selective al-adrenergic agonist phenylephrine. The maximal ven odilation induced by bradykinin was 89 +/- 5% in controls (n = 16) and 61 +/- 7% in smokers (n = 18; P = 0.02). No difference in nitroglycer in-induced venodilation was observed between the two groups. Coinfusio n of L-arginine (0.33 mg/min) markedly improved the bradykinin-induced venodilation in smokers (52 +/- 7 to 90 +/- 9%; P < 0.01). After acut e smoking cessation (n = 7), restoration to normal bradykinin-induced venodilation was observed within 24 h, whereas no change in the respon se to a maximally effective dose of nitroglycerin (1,583 ng/min) was d etected. In a human vein model appropriate for testing vascular functi onal alterations, this study demonstrates that smoking impairs endothe lium-dependent venodilation in heavy smokers. Moreover, this endotheli al dysfunction appears to be rapidly reversible after smoking cessatio n. This model may be useful in studies evaluating mechanisms of endoth elial dysfunction and interventions to modify it.