Coronary vasomotor response to the selective B1-kinin-receptor agonist Des-Arg9-bradykinin in humans.
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.
Aptecar
Eduardo
E
Fédération de Cardiologie-Hôpital Henri Mondor, INSERM-U400, Créteil, France. eaptecar@club-internet.fr
Lecorvoisier
Philippe
P
Teiger
Emmanuel
E
Garot
Philippe
P
Dupouy
Patrick
P
Sediame
Said
S
Vermes
Emmanuelle
E
Loisance
Daniel
D
Hittinger
Luc
L
Dubois-Rande
Jean-Luc
JL
Montagne
Olivier
O
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
D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D014665:Vasodilator Agents; C024626:bradykinin, des-Arg(9)-; C002385:linsidomine; D008981:Molsidomine; D000109:Acetylcholine; D001920:Bradykinin