title: Insertion-deletion polymorphism of the ACE gene modulates reversibility of endothelial dysfunction with ACE inhibition.
abstract: BACKGROUND
  The aim of this study was to examine whether angiotensin-converting enzyme (ACE) inhibition improves coronary endothelial dysfunction in patients with atherosclerosis and its risk factors and whether this was related to the ACE insertion-deletion (I/D) polymorphism.
  
  
  RESULTS
  In 56 patients with atherosclerosis or its risk factors, we studied endothelium-dependent responses with acetylcholine and endothelium-independent function with sodium nitroprusside, before and after ACE inhibition with enalaprilat. Enalaprilat did not alter either resting coronary tone or vasodilation with sodium nitroprusside. However, it potentiated the coronary microvascular and epicardial responses with acetylcholine; coronary blood flow increased from 82+/-7 to 90+/-8 mL/min (P=0.05) after enalaprilat. Patients with depressed endothelial function (P<0.001) and those with ACE DD or ID genotypes (P=0.002) but not those homozygous for the I allele had the greatest improvement by multivariate analysis. Similarly, acetylcholine-mediated epicardial vasomotion improved in segments that initially constricted (endothelial dysfunction): from -10.1+/-1% to -1.4+/-2% (P<0.001) after enalaprilat. No augmentation was observed in segments that dilated (normal endothelial dysfunction) with acetylcholine. Patients with the D allele, hypercholesterolemia, and smokers (all P<0.05) had greater improvement.
  
  
  CONCLUSIONS
  Acute ACE inhibition improves coronary epicardial and microvascular endothelium-dependent vasomotion in patients with atherosclerosis or its risk factors who have endothelial dysfunction and presence of the D allele.
authors.affiliation: Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1650, USA.
authors.forename: A
authors.initials: A
authors.lastname: Prasad
authors.forename: S
authors.initials: S
authors.lastname: Narayanan
authors.forename: S
authors.initials: S
authors.lastname: Husain
authors.forename: F
authors.initials: F
authors.lastname: Padder
authors.forename: M
authors.initials: M
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 / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics; D003326:Coronary Circulation / Q000187:drug effects / Q000235:genetics; D003327:Coronary Disease / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D015773:Enalaprilat / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009599:Nitroprusside / Q000008:administration & dosage; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D012307:Risk Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D000109:Acetylcholine