title: Angiotensin-converting enzyme inhibition improves venous endothelial dysfunction in chronic smokers.
abstract: 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 microg/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.
authors: Department of Medicine, Stanford University School of Medicine, Calif, USA.
authors: S
authors: S
authors: Chalon
authors: H
authors: H
authors: Moreno
authors: B B
authors: BB
authors: Hoffman
authors: T F
authors: TF
authors: Blaschke
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001920:Bradykinin / Q000378:metabolism*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D015773:Enalaprilat / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D012907:Smoking / Q000378:metabolism / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D014680:Veins / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D015773:Enalaprilat; D001920:Bradykinin