The role of tyrosine kinase in hypoxic constriction of sheep pulmonary artery rings.
Complex and incompletely understood mechanisms underline the vascular responses to hypoxia. Recent studies showed that the tyrosine kinase pathway is involved in vasoconstriction of vascular smooth muscle. Therefore, the aim of this study was to determine the tyrosine kinase pathway for the hypoxic contraction in large-diameter sheep pulmonary artery rings in vitro by studying the effects of selective inhibitors of tyrosine kinase and of a protein tyrosine kinase inhibitor. Lowering the pO2 from 96 to 5 mm Hg caused a contraction in arteries precontracted with 5-hydroxytryptamine (5-HT) but not under resting force. Preincubation of arteries with the tyrosine kinase inhibitors, genistein and tyrphostin, abolished the hypoxic contraction without affecting 5-HT contractions. Inhibition of tyrosine phosphatase activity by sodium orthovanadate increased the hypoxic vasoconstriction in 5-HT-precontracted arteries. These results suggest that the tyrosine kinase pathway is involved in hypoxic pulmonary vasoconstriction in sheep isolated pulmonary artery rings.
Uzun
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Department of Pharmacology, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey.
Demiryürek
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AT
Kanzik
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D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D012701:Serotonin / Q000494:pharmacology; D012756:Sheep; D013314:Stress, Mechanical; D020032:Tyrphostins / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D020032:Tyrphostins; D012701:Serotonin; D014638:Vanadates; D019833:Genistein; D011505:Protein-Tyrosine Kinases