Bradykinin mediation of Ca(2+)-activated K+ channels regulates coronary blood flow in ischemic myocardium.
BACKGROUND
Endothelium-dependent hyperpolarizing factor relaxes vascular smooth muscles by opening the Ca(2+)-activated K+ (KCa) channels. The role of the opening of KCa channels in coronary vasodilation during myocardial ischemia was investigated.


RESULTS
The left anterior descending coronary arteries of open-chest dogs were perfused with blood through an extracorporeal bypass tube from the carotid artery. Intracoronary administration of bradykinin increased coronary blood flow (CBF) in dogs treated with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase; this effect was completely inhibited by the KCa channel blocker iberiotoxin. In dogs treated with L-NAME, the bypass tube was occluded to reduce CBF to one third of the baseline value, after which coronary perfusion pressure was maintained constant. Intracoronary administration of iberiotoxin for 20 minutes further decreased CBF (from 33 +/- 2 to 19 +/- 2 mL.100 g-1.min-1, P < .01), fractional shortening, and lactate extraction ratio during coronary hypoperfusion. Bradykinin was released, and the bradykinin receptor antagonist HOE-140 blocked the effects of iberiotoxin on coronary hemodynamic and metabolic parameters during myocardial ischemia. Although the combination of L-NAME and the adenosine receptor antagonist 8-sulfophenyltheophylline reduced reactive hyperemic flow after 20 seconds of coronary occlusion, the additional presence of iberiotoxin resulted in a further decrease in this parameter.


CONCLUSIONS
The opening of KCa channels in response to endogenous bradykinin contributed to coronary vasodilation and reduced contractile and metabolic dysfunction during myocardial ischemia in open-chest dogs.
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K
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First Department of Medicine, Osaka University School of Medicine, Japan.
Kitakaze
M
M
Kosaka
H
H
Minamino
T
T
Hori
M
M
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D003326:Coronary Circulation / Q000502:physiology*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D006940:Hyperemia / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D012016:Reference Values; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D019789:Tetraethylammonium; C064719:iberiotoxin; D001920:Bradykinin; D002118:Calcium