Angiotensin-converting enzyme inhibition improves venous endothelial dysfunction in chronic smokers

Objective: In arteries and veins smoking is associated with impaired nitric oxide-mediated relaxation to endothelium-dependent agonists such as bradykinin, We investigated whether acute local angiotensin-converting enzyme (ACE) inhibition, achieved by enalaprilat, could influence bradykinin-induced vasodilation in veins of smokers. Methods: We studied 7 smokers and 7 nonsmokers with the hand vein technique. After preconstriction with phenylephrine was performed, endothelium-dependent and independent relaxations were assessed by infusing bradykinin (1 to 278 ng/min) and sodium nitroprusside (0.0001 to 3166 ng/min), respectively, Dose-response curves were constructed before and during enalaprilat coinfusion (1 mu g/min for 40 minutes), Results: Smokers had impaired venodilation to bradykinin compared with nonsmokers (P < .01), Apparent maximal relaxation induced by bradykinin was 78% +/- 9% in the control group and 48% +/- 9% in smokers (mean +/- SD). ACE inhibition shifted the bradykinin dose-response curve to the left in both groups (P < .001) and was associated with a minimal increase in apparent maximal venodilation in nonsmokers (78% +/- 9% to 83% +/- 18%), In contrast, in smokers ACE inhibition augmented the magnitude of apparent maximal venodilation to values comparable to those observed in the control group (48% +/- 9% to 102% +/- 21%), In both groups the response to sodium nitroprusside was not affected by enalaprilat. Conclusions: This study shows that acute local ACE inhibition restores bradykinin-induced relaxation in smokers to values found in nonsmokers, This observation suggests that increased vascular metabolism of bradykinin exists in veins of smokers and that the vascular renin-angiotensin system may play a key role in smoking-induced endothelial dysfunction.