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On the final 3 days of culture, myocytes were exposed to 10% O<jats:sub>2<\/jats:sub>for 3 days; control myocytes from normoxic piglets were cultured in 21% O<jats:sub>2<\/jats:sub>. PPHN was induced in newborn piglets by 3-day hypoxic exposure (Fi<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>0.10); pulmonary arterial myocytes from these animals were maintained in normoxia. Ca<jats:sup>2+<\/jats:sup>mobilization to thromboxane mimetic U-46619 and ATP was quantified using fura-2 AM. Three-day hypoxic exposure in vitro results in increased basal [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, faster and heightened peak Ca<jats:sup>2+<\/jats:sup>response, and decreased U-46619 EC<jats:sub>50<\/jats:sub>. These functional changes persist in myocytes exposed to hypoxia in vivo but cultured in 21% O<jats:sub>2<\/jats:sub>. Blockade of Ca<jats:sup>2+<\/jats:sup>entry and store refilling do not alter peak U-46619 Ca<jats:sup>2+<\/jats:sup>responses in hypoxic or normoxic myocytes. Blockade of ryanodine-sensitive or IP<jats:sub>3<\/jats:sub>-gated intracellular Ca<jats:sup>2+<\/jats:sup>channels inhibits hypoxic augmentation of peak U-46619 response. Ca<jats:sup>2+<\/jats:sup>response to ryanodine alone is undetectable; ATP-induced Ca<jats:sup>2+<\/jats:sup>mobilization is unaltered by hypoxia, suggesting no independent increase in ryanodine-sensitive or IP<jats:sub>3<\/jats:sub>-linked intracellular Ca<jats:sup>2+<\/jats:sup>pool mobilization. We conclude hypoxia has a priming effect on neonatal pulmonary arterial myocytes, resulting in increased resting Ca<jats:sup>2+<\/jats:sup>, thromboxane hypersensitivity, and hyperreactivity. We postulate that hypoxia increases agonist-induced TP-R-linked IP<jats:sub>3<\/jats:sub>pathway activation. Myocyte thromboxane hyperresponsiveness persists in culture after removal from the initiating hypoxic stimulus, suggesting altered gene expression.<\/jats:p>","DOI":"10.1152\/ajplung.00307.2005","type":"journal-article","created":{"date-parts":[[2005,10,8]],"date-time":"2005-10-08T00:13:38Z","timestamp":1128730418000},"page":"L375-L384","source":"Crossref","is-referenced-by-count":28,"title":["Hypoxia induces hypersensitivity and hyperreactivity to thromboxane receptor agonist in neonatal pulmonary arterial myocytes"],"prefix":"10.1152","volume":"290","author":[{"given":"M.","family":"Hinton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Mellow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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