title: Flow-dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs: effects of cyclooxygenase inhibition.
abstract: Endothelial damage or removal abolishes the dilation of epicardial coronary arteries induced by increments in flow through these arteries in vitro. Therefore, we tested whether or not the release of a cyclooxygenase product from endothelial cells in vivo is the mechanism of this flow-dependent dilation. In eight conscious dogs, instrumented to register the external diameter of two epicardial branches--anterior descending and circumflex--of the left coronary artery, increments in coronary flow increased and reductions in coronary flow decreased the diameter of the left circumflex epicardial artery by 182 +/- 11 micron/100% change in flow. When mean coronary flow in one epicardial branch was kept constant by a distal, flow-limiting stenosis during the application of flow-augmenting stimuli (temporal coronary occlusion or 80-400 micrograms/kg adenosine i.v.), no dilation of this artery was observed. Cyclooxygenase inhibition (suppressing the bradykinin-induced elevation of plasma 6-keto-PGF1 alpha) by indomethacin (5 mg/kg) or by diclofenac (10 mg/kg) increased smooth muscle tone in both epicardial arteries, but did not modify the flow-diameter relation (181 +/- 10 and 179 +/- 9 microns/100% change in flow, respectively). It is concluded that a tonic, instantaneous influence of coronary flow on the smooth muscle tone of the epicardial coronary arteries exists in vivo. It is unlikely that prostacyclin or another prostanoid is a mediator of this endothelium-mediated influence of flow on smooth muscle tone.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D004727:Endothelium / Q000187:drug effects; D004874:Ergonovine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D005996:Nitroglycerin; D000241:Adenosine; D004874:Ergonovine