title: The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity.
abstract: OBJECTIVE
  We investigated whether the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene modulates vasomotor tone and endothelial function.
  
  
  BACKGROUND
  The deletion allele of the ACE I/D polymorphism has been associated with increased incidence of cardiovascular pathology. The risk is synergistically increased in patients who also possess the C allele at position 1,166 of the angiotensin type I (AT1) receptor gene.
  
  
  METHODS
  In 177 patients with coronary atherosclerosis or its risk factors, we investigated endothelial function with intracoronary acetylcholine (ACH), endothelium-independent smooth muscle function with sodium nitroprusside (SNP) and basal nitric oxide activity with L-NG monomethyl arginine.
  
  
  RESULTS
  Compared with ACE II genotype, patients with the ACE DD genotype had lower coronary microvascular and epicardial responses with SNP (coronary blood flow increase 196 +/- 26% vs. 121 +/- 11%, p = 0.003, and diameter increase 21.9 +/- 2% vs. 17 +/- 1%, p = 0.03, ACE II vs. DD, respectively). L-NG monomethyl arginine induced greater constriction in patients with the ACE DD compared with ACE II genotype (coronary blood flow -10 +/- 4% vs. 11 +/- 5%, p = 0.003, ACE DD vs. II and diameter constriction -6.3 +/- 1.2% vs. -1.9 +/- 1.2%, p = 0.01, respectively, in patients with atherosclerosis). No difference in ACH-mediated vasomotion was detected between the three ACE genotypes. The AT1 receptor polymorphism did not influence responses to either SNP or ACH.
  
  
  CONCLUSIONS
  Patients possessing the D allele of the ACE gene have increased vascular smooth muscle tone. The enhanced tone appears to be counterbalanced by an increase in basal nitric oxide activity in patients with atherosclerosis.
authors.affiliation: Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
authors.forename: A
authors.initials: A
authors.lastname: Prasad
authors.forename: S
authors.initials: S
authors.lastname: Narayanan
authors.forename: M A
authors.initials: MA
authors.lastname: Waclawiw
authors.forename: N
authors.initials: N
authors.lastname: Epstein
authors.forename: A A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000235:genetics* / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009129:Muscle Tonus / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A; D000109:Acetylcholine