{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:12:20Z","timestamp":1781629940535,"version":"3.54.5"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,6,4]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Nitrosation of a conserved cysteine residue at position 93 in the hemoglobin \u03b2 chain (\u03b293C) to form S-nitroso (SNO) hemoglobin (Hb) is claimed to be essential for export of nitric oxide (NO) bioactivity by the red blood cell (RBC) to mediate hypoxic vasodilation and cardioprotection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>To test this hypothesis, we used RBCs from mice in which the \u03b293 cysteine had been replaced with alanine (\u03b293A) in a number of ex vivo and in vivo models suitable for studying export of NO bioactivity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>In an ex vivo model of cardiac ischemia\/reperfusion injury, perfusion of a mouse heart with control RBCs (\u03b293C) pretreated with an arginase inhibitor to facilitate export of RBC NO bioactivity improved cardiac recovery after ischemia\/reperfusion injury, and the response was similar with \u03b293A RBCs. Next, when human platelets were coincubated with RBCs and then deoxygenated in the presence of nitrite, export of NO bioactivity was detected as inhibition of ADP-induced platelet activation. This effect was the same in \u03b293C and \u03b293A RBCs. Moreover, vascular reactivity was tested in rodent aortas in the presence of RBCs pretreated with S-nitrosocysteine or with hemolysates or purified Hb treated with authentic NO to form nitrosyl(FeII)-Hb, the proposed precursor of SNO-Hb. SNO-RBCs or NO-treated Hb induced vasorelaxation, with no differences between \u03b293C and \u03b293A RBCs. Finally, hypoxic microvascular vasodilation was studied in vivo with a murine dorsal skin-fold window model. Exposure to acute systemic hypoxia caused vasodilatation, and the response was similar in \u03b293C and \u03b293A mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>RBCs clearly have the fascinating ability to export NO bioactivity, but this occurs independently of SNO formation at the \u03b293 cysteine of Hb.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.118.039284","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T09:00:17Z","timestamp":1553504417000},"page":"2654-2663","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Hemoglobin \u03b293 Cysteine Is Not Required for Export of Nitric Oxide Bioactivity From the Red Blood Cell"],"prefix":"10.1161","volume":"139","author":[{"given":"Chiao-Wang","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Biochemistry (C.W.S., T.T.), University of Alabama at Birmingham."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangning","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (J.Y., J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei L.","family":"Kleschyov","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (A.L.K., Z.Z., M.C., J.O.L.)."},{"name":"Freiberg Instruments GmbH, Freiberg, Germany (A.L.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengbing","family":"Zhuge","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (A.L.K., Z.Z., M.C., J.O.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Carlstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (A.L.K., Z.Z., M.C., J.O.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pernow","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (J.Y., J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem","family":"Wajih","sequence":"additional","affiliation":[{"name":"Department of Physics, Wake Forest University, Winston-Salem, NC (N.W., D.B.K.-S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Scott","family":"Isbell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saint Louis University, MO (T.S.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo-Yeun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pathology (J.-Y.O., R.P.P.), University of Alabama at Birmingham."},{"name":"Center for Free Radical Biology (J.-Y.O., R.P.P.), University of Alabama at Birmingham."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Cabrales","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California San Diego (P.C., A.G.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy G.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California San Diego (P.C., A.G.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Townes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (C.W.S., T.T.), University of Alabama at Birmingham."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Kim-Shapiro","sequence":"additional","affiliation":[{"name":"Department of Physics, Wake Forest University, Winston-Salem, NC (N.W., D.B.K.-S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh P.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pathology (J.-Y.O., R.P.P.), University of Alabama at Birmingham."},{"name":"Center for Free Radical Biology (J.-Y.O., R.P.P.), University of Alabama at Birmingham."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon O.","family":"Lundberg","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (A.L.K., Z.Z., M.C., J.O.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/380221a0"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm718"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/35054560"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2034"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c090009"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi960442g"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2006.11.002"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.060603.090918"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-442277"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1307058110"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2018.03.006"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.05.052"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030380"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.609222"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1771"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90425"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1502285112"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1008-1008"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.2007.01690.x"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1067\/mtc.2003.36"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.05.014"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0880"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.22.15487"},{"key":"e_1_3_4_25_2","first-page":"1055","article-title":"Dorsal skinfold chamber technique for intravital microscopy in nude mice.","volume":"143","author":"Lehr HA","year":"1993","unstructured":"Lehr, HA, Leunig, M, Menger, MD, Nolte, D, Messmer, K. 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