{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:32:02Z","timestamp":1790854322332,"version":"4.1.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"41","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,10,11]]},"abstract":"<jats:p>\n                    The mechanism by which hypoxia [low partial pressure of O\n                    <jats:sub>2<\/jats:sub>\n                    (pO\n                    <jats:sub>2<\/jats:sub>\n                    )] elicits signaling to regulate pulmonary arterial pressure is incompletely understood. We considered the possibility that, in addition to its effects on smooth muscle, hypoxia may influence pulmonary vascular tone through an effect on RBCs. We report that exposure of native RBCs to sustained hypoxia is accompanied by a buildup of heme iron-nitrosyl (FeNO) species that are deficient in pO\n                    <jats:sub>2-<\/jats:sub>\n                    governed intramolecular transfer of NO to cysteine thiol, yielding a deficiency in the vasodilator\n                    <jats:italic>S<\/jats:italic>\n                    -nitrosohemoglobin (SNO-Hb).\n                    <jats:italic>S<\/jats:italic>\n                    -nitrosothiol (SNO)-deficient RBCs produce impaired vasodilator responses\n                    <jats:italic>in vitro<\/jats:italic>\n                    and exaggerated pulmonary vasoconstrictor responses\n                    <jats:italic>in vivo<\/jats:italic>\n                    and are defective in oxygenating the blood. RBCs from hypoxemic patients with elevated pulmonary arterial pressure (PAP) exhibit a similar FeNO\/SNO imbalance and are thus deficient in pO\n                    <jats:sub>2<\/jats:sub>\n                    -coupled vasoregulation. Chemical restoration of SNO-Hb levels in both animals and patients restores the vasodilator activity of RBCs, and this activity is associated with improved oxygenation and lower PAPs.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0506957102","type":"journal-article","created":{"date-parts":[[2005,10,3]],"date-time":"2005-10-03T20:33:35Z","timestamp":1128371615000},"page":"14801-14806","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":122,"title":["A nitric oxide processing defect of red blood cells created by hypoxia: Deficiency of S-nitrosohemoglobin in pulmonary hypertension"],"prefix":"10.1073","volume":"102","author":[{"given":"Timothy J.","family":"McMahon","sequence":"first","affiliation":[{"name":"Departments of Medicine and Pediatrics and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710; and Department of Chemistry, Montana State University, Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Ahearn","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710; and Department of Chemistry, Montana State University, Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin P.","family":"Moya","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710; and Department of Chemistry, Montana State University, Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Gow","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710; and Department of Chemistry, Montana State University, Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuh-Chin T.","family":"Huang","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710; and Department of Chemistry, Montana State University, Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin P.","family":"Luchsinger","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710; and Department of Chemistry, Montana State University, Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Nudelman","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710; and Department of Chemistry, Montana State University, Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yan","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710; 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