title: Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans.
abstract: OBJECTIVE
  The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors.
  
  
  BACKGROUND
  Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone.
  
  
  METHODS
  In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 microg/min) and BK (62.5 ng/min and 4 microg/min), and endothelium-independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin-converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed.
  
  
  RESULTS
  There was progressive impairment in ACH-mediated microvascular dilation with increasing numbers of risk factors (p = 0.025, analysis of variance). By contrast, BK- and sodium nitroprusside-mediated microvascular dilation was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK; segments that constricted or dilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constricted with pacing. Finally, epicardial BK responses were depressed in patients with high ACE levels and in those with the ACE DD genotype.
  
  
  CONCLUSIONS
  Endothelial dysfunction in atherosclerosis appears to be receptor-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteries during physiologic stress is better represented by BK and not by ACH responses. Bradykinin activity and, hence, physiologic coronary vasomotion appears to be influenced by serum ACE levels and the ACE insertion/deletion genotype.
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: Husain
authors.forename: W
authors.initials: W
authors.lastname: Schenke
authors.forename: R
authors.initials: R
authors.lastname: Mincemoyer
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; D000241:Adenosine / Q000494:pharmacology; D001161:Arteriosclerosis / Q000503:physiopathology*; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000502:physiology*; D012307:Risk Factors; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D018002:Receptors, Bradykinin; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A; D000241:Adenosine; D000109:Acetylcholine; D001920:Bradykinin