Effect of 15-HETE on potassium channels of rabbit pulmonary arterial smooth muscles during hypoxia.
This study investigated the role of 15-hydroxyeicosatetraenoic acid (15-HETE) in rabbit pulmonary arterial smooth muscle cells (PASMCs) under hypoxia by using organ bath and whole cell patch-clamp techniques. Neonatal rabbits born into normoxic environment were transferred after first feeding into normal and hypoxic environments with respectively 0.21 and 0.12 fractional inspired oxygen (FiO2). Pulmonary arteries were extracted after 9 d and cut into rings 1.0 approximately 1.5 mm in length for organ bath experiments. Whole cell patch-clamp technique was used to measure the potassium current in the freshly dispersed rabbit PASMCs. The results showed that 15-HETE-induced vasoconstriction was blocked by 4-aminopyridine (5 mmol/L), a Kv channel blocker. The K(ATP) channel blocker glyburide (1 micromol/L) and the BKCa channel blocker tetraethylammonium (10 mmol/L) did not abolish this vasoconstriction. 15-HETE decreased the whole-cell voltage-gated K+ current in the PASMCs. These findings demonstrate that hypoxia blocks Kv channels through a 15-HETE mediated mechanism, leading to PA vasoconstriction.
Han
Wei-Na
WN
College of Pharmacy, Harbin Medical University, Harbin 150086, China.
Li
Xiang-Hui
XH
Jiang
Zhu-Ying
ZY
Ji
Hong-Yu
HY
Huang
Li-Jun
LJ
Wang
Zhi-Min
ZM
Zhu
Da-Ling
DL
D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia; D002478:Cells, Cultured; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects; D011247:Pregnancy; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D006893:Hydroxyeicosatetraenoic Acids; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D014662:Vasoconstrictor Agents; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid