Inhibition of prostanoid-mediated contraction to endothelin-1 after hypoxia in rat aorta.
The role of the thromboxane A(2)/prostaglandin H(2) receptor in endothelin-1 contraction was investigated in aortic rings from rats exposed to normoxia (21% O(2)) or hypoxia (10% O(2)) for 12 h. Indomethacin (10 microM) and SQ 29,548 (0.1 microM, thromboxane A(2)/prostaglandin H(2) receptor antagonist) reduced maximum tension and increased EC(50) in endothelium-intact and -denuded rings from normoxic animals. Neither inhibitor had any effect on rings from hypoxic rats. Thromboxane A(2) and/or prostaglandin H(2) contribute to the response to endothelin-1 in aortas from normoxic rats but not from rats exposed to hypoxia. Loss of prostanoid-enhancement of endothelin-1 contraction contributes to impair vascular reactivity after hypoxia.
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Division of Respirology and Terrence Donnelly Research Laboratories, St. Michael's Hospital, Rm. 6042 Bond Wing, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8.
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000502:physiology*; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D019332:Endothelin-1; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011982:Receptors, Prostaglandin; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; C045749:SQ 29548; D000109:Acetylcholine