title: The role of Na(+), K(+)-ATPase in the hypoxic vasoconstriction in isolated rat basilar artery.
abstract: Hypoxia-induced cerebrovascular dysfunction is a key factor in the occurrence and the development of cerebral ischemia. Na(+), K(+)-ATPase affects the regulation of intracellular Ca(2+) concentration and plays an important role in vascular smooth muscle function. However, the potential role of Na(+), K(+)-ATPase in hypoxia-induced cerebrovascular dysfunction is unknown. In this study, we found that the KCl-induced contraction under hypoxia in rat endothelium-intact basilar arteries is similar to that of denuded arteries, suggesting that hypoxia may cause smooth muscle cell (SMC)-dependent vasoconstriction in the basilar artery. The Na(+), K(+)-ATPase activity of the isolated basilar artery with or without endothelium significantly reduced with prolonged hypoxia. Blocking the Na(+)-Ca(2+) exchanger with Ni(2+) (10(-3)M) or the L-type Ca(2+) channel with nimodipine (10(-8)M) dramatically attenuated KCl-induced contraction under hypoxia. Furthermore, prolonged hypoxia significantly reduced Na(+), K(+)-ATPase activity and increased [Ca(2+)]i in cultured rat basilar artery SMCs. Hypoxia reduced the protein and mRNA expression of the α2 isoform of Na(+), K(+)-ATPase in SMCs in vitro. We used a low concentration of the Na(+), K(+)-ATPase inhibitor ouabain, which possesses a high affinity for the α2 isoform. The contractile response in the rat basilar artery under hypoxia was partly inhibited by ouabain pretreatment. The decreased Na(+), K(+)-ATPase activity in isolated basilar artery and the increased [Ca(2+)]i in SMCs induced by hypoxia were partly inhibited by pretreatment with a low concentration of ouabain. These results suggest that hypoxia may educe Na(+), K(+)-ATPase activity in SMCs through the α2 isoform contributing to vasoconstriction in the rat basilar artery.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China; Lab of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China. Electronic address: lping77@hotmail.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Lv
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000201:enzymology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000494:pharmacology; D020013:Calcium Signaling; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D014662:Vasoconstrictor Agents; C498532:Atp1a2 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Basilar artery; Calcium; Hypoxia; Na(+), K(+)-ATPase