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 bradyk inin, We investigated whether acute local angiotensin-converting enzyme (AC E) 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-depen dent 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 coinf usion (1 mu g/min for 40 minutes), Results: Smokers had impaired venodilation to bradykinin compared with nons mokers (P < .01), Apparent maximal relaxation induced by bradykinin was 78% +/- 9% in the control group and 48% +/- 9% in smokers (mean +/- SD). ACE i nhibition shifted the bradykinin dose-response curve to the left in both gr oups (P < .001) and was associated with a minimal increase in apparent maxi mal venodilation in nonsmokers (78% +/- 9% to 83% +/- 18%), In contrast, in smokers ACE inhibition augmented the magnitude of apparent maximal venodil ation to values comparable to those observed in the control group (48% +/- 9% to 102% +/- 21%), In both groups the response to sodium nitroprusside wa s not affected by enalaprilat. Conclusions: This study shows that acute local ACE inhibition restores brad ykinin-induced relaxation in smokers to values found in nonsmokers, This ob servation 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.