Flow-dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs: effects of cyclooxygenase inhibition.

TLDR

In vitro, endothelial damage abolishes flow‑induced dilation of epicardial coronary arteries. The study aimed to determine whether endothelial cyclooxygenase products mediate flow‑dependent dilation in vivo. Eight conscious dogs were instrumented to measure external diameters of the left anterior descending and circumflex arteries; flow increases raised circumflex diameter by ~182 µm per 100 % flow change, while constant flow during flow‑augmenting stimuli prevented dilation, and COX inhibition raised tone but did not alter the flow‑diameter relationship. The data show a tonic, instantaneous influence of coronary flow on epicardial smooth‑muscle tone, but prostacyclin or other prostanoids are unlikely mediators.

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.