{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:46:22Z","timestamp":1790923582597,"version":"4.1.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1995,7]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            Dithionite is a powerful reducing agent used to deoxygenate hemoglobin and create anaerobic conditions in vitro. Recently, dithionite has been used as a convenient means of creating \u201chypoxia\u201d in experiments studying the O\n            <jats:sub>2<\/jats:sub>\n            sensor in the pulmonary circulation and carotid body. We evaluated the hypothesis that hypoxia created by hypoxic ventilation and that created by dithionite have different effects on the pulmonary circulation. In vitro, dithionite (10\n            <jats:sup>\u22125<\/jats:sup>\n            to 10\n            <jats:sup>\u22123<\/jats:sup>\n            mol\/L), added to oxygenated Krebs\u2019 solution, rapidly created superoxide anion in a dose-dependent manner. Dithionite consumed O\n            <jats:sub>2<\/jats:sub>\n            in parallel with the generation of superoxide radical, with both processes peaking within seconds. Anoxia was sustained only if resupply of O\n            <jats:sub>2<\/jats:sub>\n            was prevented. In isolated rat lungs (whether perfused with autologous blood or Krebs\u2019 solution), hypoxic ventilation alone lowered perfusate P\n            <jats:sc>o<\/jats:sc>\n            <jats:sub>2<\/jats:sub>\n            from \u2248140 to 40 mm Hg and decreased lung levels of activated oxygen species (AOS), measured by luminol-enhanced chemiluminescence, before the onset of hypoxic pulmonary vasoconstriction. Constrictor responses to angiotensin II and KCl were not impaired by intermittent hypoxic challenges, and lung weight did not increase. In contrast, dithionite impaired constrictor responses of the Krebs\u2019 solution\u2013perfused lungs to all vasoconstrictors tested and increased lung weight. When given as a bolus (5\u00d710\n            <jats:sup>\u22123<\/jats:sup>\n            mol\/L) into the pulmonary artery during normoxic ventilation, dithionite caused no vasoconstriction and only briefly lowered P\n            <jats:sc>o<\/jats:sc>\n            <jats:sub>2<\/jats:sub>\n            (because of constant resupply of O\n            <jats:sub>2<\/jats:sub>\n            from the alveoli). When superimposed on hypoxic ventilation, dithionite further lowered P\n            <jats:sc>o<\/jats:sc>\n            <jats:sub>2<\/jats:sub>\n            from \u224840 to \u22480 mm Hg and caused additional constriction. Unlike hypoxic ventilation, dithionite increased AOS production. Antioxidant enzymes diminished dithionite-induced radical production and diminished the loss of vascular reactivity and lung edema. In conclusion, unlike hypoxic ventilation, dithionite causes edema and loss of vascular reactivity in the lung by generating superoxide anion and hydrogen peroxide. Hypoxia elicited by dithionite is not equivalent to authentic hypoxia because of the obligatory associated generation of AOS. Dithionite usage should not be substituted for authentic hypoxia in studies of O\n            <jats:sub>2<\/jats:sub>\n            sensing.\n          <\/jats:p>","DOI":"10.1161\/01.res.77.1.174","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"174-181","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Dithionite Increases Radical Formation and Decreases Vasoconstriction in the Lung"],"prefix":"10.1161","volume":"77","author":[{"given":"Stephen L.","family":"Archer","sequence":"first","affiliation":[{"name":"From the Minneapolis Veterans Affairs Medical Center and the University of Minnesota, Minneapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Va\u0301clav","family":"Hampl","sequence":"additional","affiliation":[{"name":"From the Minneapolis Veterans Affairs Medical Center and the University of Minnesota, Minneapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Nelson","sequence":"additional","affiliation":[{"name":"From the Minneapolis Veterans Affairs Medical Center and the University of Minnesota, Minneapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Sidney","sequence":"additional","affiliation":[{"name":"From the Minneapolis Veterans Affairs Medical Center and the University of Minnesota, Minneapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Peterson","sequence":"additional","affiliation":[{"name":"From the Minneapolis Veterans Affairs Medical Center and the University of Minnesota, Minneapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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