Role of endogenous bradykinin in human coronary vasomotor control.
BACKGROUND
Bradykinin is a potent vasodilator that acts through B2 kinin receptors to stimulate the release of endothelium-derived nitric oxide, prostacyclin, and hyperpolarizing factor. In this study, we investigated the contribution of endogenous bradykinin to vasomotor control in the human coronary circulation.


RESULTS
The selective bradykinin B2 receptor antagonist HOE 140 was infused into the left main coronary artery (200 micrograms/min for 15 minutes) in 15 patients without significant coronary stenoses. Epicardial responses were evaluated by quantitative coronary blood flow with a Doppler flow-velocity wire. Flow-dependent dilation (n = 10; intracoronary papaverine) and acetylcholine responses (n = 5) were assessed before and after HOE 140. After HOE 140, there was a reduction in luminal area in the proximal (P < .001), mid (P < .001), and distal (P < .05) coronary arteries. HOE 140 led to an increase in coronary vascular resistance (P < .001) and a decrease in coronary blood flow (P < .001). After bradykinin B2 receptor blockade, there was a reduction in flow-dependent dilation (23.4 +/- 6.9% to 3.9 +/- 6.0%, P < .001), the extent of which correlated with the degree of basal vasoconstriction after HOE 140 in the same vessel segment (P < .05). Acetylcholine responses were unchanged after HOE 140.


CONCLUSIONS
The results of this study demonstrate for the first time a role for endogenous bradykinin in mediating normal vasomotor responses in resistance and epicardial coronary vessels under basal and flow-stimulated conditions in the human coronary circulation.
Medizinische Klinik III, Universität Freiburg, Germany.
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P
Groves
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S
Kurz
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H
Just
H
H
Drexler
D000818:Animals; D001783:Blood Flow Velocity; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D002417:Cattle; D002478:Cells, Cultured; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D065168:Bradykinin Receptor Antagonists; C065679:icatibant; D019001:Nitric Oxide Synthase; D001920:Bradykinin