{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:59:35Z","timestamp":1773723575691,"version":"3.50.1"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2002,7,1]],"date-time":"2002-07-01T00:00:00Z","timestamp":1025481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Endothelin-1 (ET-1) mediates the development of pulmonary hypertension (PHT) in newborn rats exposed to 60% O2 for 14 days, a model for human chronic neonatal lung injury. ET-1 production by d-14 rat pulmonary artery smooth muscle cells in vitro was markedly increased by thromboxane (TX) A2 receptor agonists and inhibited by a competitive antagonist. We hypothesized that stimulation of the TX A2 receptor contributed to O2-mediated PHT in vivo. Newborn rat pups received daily intraperitoneal injections of L670596, a competitive TX A2 receptor antagonist, or 5,5-dimethyl-3-(3-fluorophenyl)4-(4-methylsulfonyl)phenyl-2(5H)-furanone (DFU), a cyclooxygenase-2 inhibitor, during 14 days of 60% O2 or air exposure. L670596, but not DFU, prevented 60% O2\u2013mediated right ventricular and small pulmonary vessel smooth muscle hypertrophy. Lung ET-1 content was significantly reduced by L670596 in 60% O2\u2013exposed animals. We conclude that TX A2 receptor activation, though not by TX A2, caused upregulation of ET-1 and PHT in this model. A likely mediator is the stable lipid peroxidation product, 8-iso-prostane, which acts as an incidental ligand of the TX A2 receptor and is a potent inducer of ET-1 production by cultured d-14 rat pulmonary artery smooth muscle cells in vitro.<\/jats:p>","DOI":"10.1164\/rccm.200112-124oc","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T19:17:19Z","timestamp":1027883839000},"page":"208-214","source":"Crossref","is-referenced-by-count":38,"title":["Thromboxane A2 Receptors Mediate Pulmonary Hypertension in 60% Oxygen\u2013exposed Newborn Rats by a Cyclooxygenase-independent Mechanism"],"prefix":"10.1093","volume":"166","author":[{"given":"Robert P.","family":"Jankov","sequence":"first","affiliation":[{"name":"Canadian Institutes of Health Research (CIHR) Group in Lung Development, Lung Biology Programme; Division of Cardiovascular Research, Hospital for Sick Children Research Institute; CIHR Group in Developmental and Fetal Health, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital; and Departments of Obstetrics and Gynaecology, Paediatrics, and Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}]},{"given":"Rosetta","family":"Belcastro","sequence":"additional","affiliation":[{"name":"Canadian Institutes of Health Research (CIHR) Group in Lung Development, Lung Biology Programme; Division of Cardiovascular Research, Hospital for Sick Children Research Institute; CIHR Group in Developmental and Fetal Health, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital; and Departments of Obstetrics and Gynaecology, Paediatrics, and Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}]},{"given":"Emira","family":"Ovcina","sequence":"additional","affiliation":[{"name":"Canadian Institutes of Health Research (CIHR) Group in Lung Development, Lung Biology Programme; Division of Cardiovascular Research, Hospital for Sick Children Research Institute; CIHR Group in Developmental and Fetal Health, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital; and Departments of Obstetrics and Gynaecology, Paediatrics, and Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}]},{"given":"Julia","family":"Lee","sequence":"additional","affiliation":[{"name":"Canadian Institutes of Health Research (CIHR) Group in Lung Development, Lung Biology Programme; Division of Cardiovascular Research, Hospital for Sick Children Research Institute; CIHR Group in Developmental and Fetal Health, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital; and Departments of Obstetrics and Gynaecology, Paediatrics, and Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}]},{"given":"Hamid","family":"Massaeli","sequence":"additional","affiliation":[{"name":"Canadian Institutes of Health Research (CIHR) Group in Lung Development, Lung Biology Programme; Division of Cardiovascular Research, Hospital for Sick Children Research Institute; CIHR Group in Developmental and Fetal Health, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital; and Departments of Obstetrics and Gynaecology, Paediatrics, and Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}]},{"given":"Stephen J.","family":"Lye","sequence":"additional","affiliation":[{"name":"Canadian Institutes of Health Research (CIHR) Group in Lung Development, Lung Biology Programme; Division of Cardiovascular Research, Hospital for Sick Children Research Institute; CIHR Group in Developmental and Fetal Health, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital; and Departments of Obstetrics and Gynaecology, Paediatrics, and Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}]},{"given":"A. 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