Mechanism of coronary vasodilation produced by bradykinin.
BACKGROUND
Bradykinin has been demonstrated to be an endothelium-dependent vasodilator in the cerebral circulation of the mouse, but the actions of bradykinin on regional tissue perfusion in the canine coronary circulation have not been studied.


RESULTS
The mechanism of coronary vasodilation by bradykinin was studied in open-chest, anesthetized dogs. The role of cyclooxygenase stimulation, bradykinin B2 receptor activation, and endothelium-derived relaxing factor in bradykinin-mediated vasodilation was studied in separate groups of dogs. Bradykinin was infused intracoronarily so as to avoid changes in systemic hemodynamics capable of altering the regional distribution of coronary blood flow (radioactive microspheres). Bradykinin produced a preferential increase in subendocardial blood flow. Pretreatment with indomethacin had no effect on bradykinin-mediated increases in total left ventricular flow or the transmural distribution of coronary blood flow. Blockade of bradykinin B2 receptors with the competitive antagonist [Thi5,8, D-Phe7]-bradykinin attenuated both the increase in total flow and redistribution of perfusion to the subendocardium produced by bradykinin. Inhibition of endothelium-derived relaxing factor with quinacrine, occlusion/reperfusion, or NG-monomethyl L-arginine attenuated the total increase in left ventricular flow and blocked the redistribution of flow to the subendocardium produced by bradykinin.


CONCLUSIONS
The present results demonstrate that intracoronary infusion of bradykinin produces a preferential increase in blood flow to the subendocardium via stimulation of B2 receptors and the release of an endothelium-dependent relaxing factor that may be nitric oxide.
Pelc
L R
LR
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Gross
G J
GJ
Warltier
D C
DC
D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000494:pharmacology*
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001920:Bradykinin