title: Methylene blue and ETYA block flow-dependent dilation in canine femoral artery.
abstract: Flow-dependent dilation of the canine femoral artery is endothelial cell dependent and is not mediated by prostaglandins, adrenergic or cholinergic receptors, an ascending message from the microcirculation, or by myogenic mechanisms. We investigated the mechanism of flow dilation in 38 pentobarbital anesthetized dogs. A femoral artery-jugular vein shunt was constructed, and femoral artery diameter was continuously measured (sonomicrometer crystals) during control and maximum flow (1 l/min). Inhibition of prostaglandin formation by indomethacin did not alter the dilation response to increased flow, but the lipoxygenase-cyclooxygenase inhibitor 5, 8, 11, 14 eicosatetraynoic acid (ETYA) irreversibly inhibited the dilation response to increased flow. The guanylate cyclase inhibitor, methylene blue, caused a dose-dependent decrease in the dilation response to increased flow. Pretreatment with the H1 receptor antagonist tripelennamine sensitized the vessel to the inhibitory effects of methylene blue. Both methylene blue and ETYA shifted the ED50 for acetylcholine relaxation two orders of magnitude to the right, but did not alter the ability of the vessel to dilate or constrict to other stimuli. These data suggest that both cyclic GMP and a non-prostaglandin metabolite of arachidonic acid are involved in flow dilation. We propose that endothelial cells release a metabolite of arachidonic acid that stimulates vascular smooth muscle guanylate cyclase leading to relaxation. The role of histamine in this system is unknown.
mesh_terms: D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D006152:Cyclic GMP / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D005263:Femoral Artery / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D012039:Regional Blood Flow; D014309:Tripelennamine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D014309:Tripelennamine; D006632:Histamine; D006152:Cyclic GMP; D000109:Acetylcholine; D008751:Methylene Blue; D007213:Indomethacin