Hypoxia-induced 15-HETE enhances the constriction of internal carotid arteries by down-regulating potassium channels.
Severe hypoxia induces the constriction of internal carotid arteries (ICA), which worsens ischemic stroke in the brain. A few metabolites are presumably involved in hypoxic vasoconstriction, however, less is known about how such molecules provoke this vasoconstriction. We have investigated the influence of 15-hydroxyeicosatetrienoic acid (15-HETE) produced by 15-lipoxygenase (15-LOX) on vasoconstriction during hypoxia. As showed in our results, 15-LOX level increases in ICA endothelia and smooth muscles. 15-HETE enhances the tension of ICA ring in a dose-dependent manner, as well as attenuates the activities and expression of voltage-gated potassium channels (Kv 1.5 and Kv 2.1). Therefore, the down-regulation of Kv channels by 15-HETE during hypoxia may weaken the repolarization of action potentials and causes a dominant influx of calcium ions to enhance smooth muscle tension and ICA constriction.
Zhu
Yanmei
Y
Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, China.
Chen
Li
L
Liu
Wenjuan
W
Wang
Weizhi
W
Zhu
Daling
D
Zhu
Yulan
Y
D000704:Analysis of Variance; D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D002339:Carotid Arteries / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D015221:Potassium Channels; D012333:RNA, Messenger; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase