title: Coronary vasomotor response to the selective B1-kinin-receptor agonist Des-Arg9-bradykinin in humans.
abstract: OBJECTIVE
  The aim of the present study was to assess the effects of selective B1-receptor stimulation with des-Arg9-bradykinin on coronary vasomotion in transplanted and non-transplanted patients.
  
  
  BACKGROUND
  Bradykinin B1-receptors have been identified on endothelial and smooth muscle cells in human coronary arteries in vitro; however, their physiologic role in the coronary circulation is unknown.
  
  
  METHODS
  Twelve heart transplant patients were compared with 10 control subjects at 3.2 +/- 2.2 months after surgery. Coronary flow velocity was measured using guide-wire Doppler. The diameter of 3 epicardial segments of the left coronary artery and coronary blood flow were assessed at baseline, immediately after infusions of increasing doses of des-arginine(Arg9)-bradykinin at estimated coronary blood concentrations of 5.4 x 10(-9), 5.4 x 10(-8), 5.4 x 10(-7) and 1.6 x 10(-6) mol/liter, and of acetylcholine at 10(-8), 10(-7) and 10(-6) mol/liter).
  
  
  RESULTS
  Des-Arg9-bradykinin induced a similar decrease in all measured epicardial diameters in both groups and no change in coronary blood flow. Vasoconstriction was significant only at the 2 highest concentrations: -6 +/- 9% (p < 0.01) and -7 +/- 11% (p < 0.01) in control subjects, and -8 +/- 8% (p < 0.001) and -9 +/- 11% (p < 0.001) in heart transplant patients. Acetylcholine induced significant epicardial vasodilation in control subjects and vasoconstriction in transplant patients. The presence of allograft rejection did not modify the responses to des-Arg9-bradykinin with regard to both conductance and resistance vessels.
  
  
  CONCLUSIONS
  Kinin B1-receptors exist and can be stimulated in humans. The vasoconstrictive action on epicardial coronary arteries of des-Arg(9)-bradykinin in humans argues for a predominant action of B1-receptor stimulation at the level of smooth muscle cells.
authors.affiliation: Fédération de Cardiologie-Hôpital Henri Mondor, INSERM-U400, Créteil, France. eaptecar@club-internet.fr
authors.forename: Eduardo
authors.initials: E
authors.lastname: Aptecar
authors.forename: Philippe
authors.initials: P
authors.lastname: Lecorvoisier
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Teiger
authors.forename: Philippe
authors.initials: P
authors.lastname: Garot
authors.forename: Patrick
authors.initials: P
authors.lastname: Dupouy
authors.forename: Said
authors.initials: S
authors.lastname: Sediame
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Vermes
authors.forename: Daniel
authors.initials: D
authors.lastname: Loisance
authors.forename: Luc
authors.initials: L
authors.lastname: Hittinger
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dubois-Rande
authors.forename: Olivier
authors.initials: O
authors.lastname: Montagne
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000737:chemistry / Q000502:physiology; D005260:Female; D016027:Heart Transplantation / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000502:physiology; D043783:Receptor, Bradykinin B1 / Q000819:agonists* / Q000032:analysis / Q000502:physiology*; D043782:Receptor, Bradykinin B2 / Q000819:agonists* / Q000032:analysis / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D014665:Vasodilator Agents; C024626:bradykinin, des-Arg(9)-; C002385:linsidomine; D008981:Molsidomine; D000109:Acetylcholine; D001920:Bradykinin