{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:07:07Z","timestamp":1789963627631,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,4,23]],"date-time":"2015-04-23T00:00:00Z","timestamp":1429747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["HL058091"],"award-info":[{"award-number":["HL058091"]}]},{"name":"NIH","award":["HL098032"],"award-info":[{"award-number":["HL098032"]}]},{"name":"NIH","award":["T32 GM095440"],"award-info":[{"award-number":["T32 GM095440"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Sickle cell disease (SCD) is characterized by hemoglobin polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium\u2010activated Gardos channel, which dehydrates the cells leading to increased polymerization. In this study the effects of nitric oxide (NO) and its congeners on RBC deformability were examined, focusing on sickle RBCs (sRBCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>RBCs from patients with SCD and from nonpatients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sRBCs. Deformability was measured by laser\u2010assisted osmotic gradient ektacytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium\u2010induced loss of deformability in normal RBCs, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation\u2010induced dehydration of sRBCs, SNP resulted in substantial improvements in deformability (p\u2009=\u20090.036) and hydration (p\u2009=\u20090.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>These data suggest that SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.13134","type":"journal-article","created":{"date-parts":[[2015,4,23]],"date-time":"2015-04-23T09:21:21Z","timestamp":1429780881000},"page":"2464-2472","source":"Crossref","is-referenced-by-count":35,"title":["Effects of nitric oxide and its congeners on sickle red blood cell deformability"],"prefix":"10.1111","volume":"55","author":[{"given":"Andrea M.","family":"Belanger","sequence":"first","affiliation":[{"name":"Department of Physics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Keggi","sequence":"additional","affiliation":[{"name":"Department of Physics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamir","family":"Kanias","sequence":"additional","affiliation":[{"name":"Heart, Lung, Blood and Vascular Medicine Institute"},{"name":"Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Gladwin","sequence":"additional","affiliation":[{"name":"Heart, Lung, Blood and Vascular Medicine Institute"},{"name":"Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Kim\u2010Shapiro","sequence":"additional","affiliation":[{"name":"Department of Physics"},{"name":"Translational Science Center, Wake Forest University Winston\u2010Salem North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199709113371107"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111672"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(94)90003-5"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200203000-00004"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(85)90174-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(85)90175-5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm070663s"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.7.2551"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.7.2594"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-228577"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152509787047649"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00665.2002"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-3992"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12291"},{"key":"e_1_2_7_16_1","volume-title":"Nitrosation 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