title: Regulation of red blood cell deformability is independent of red blood cell-nitric oxide synthase under hypoxia.
abstract: The aim was to study impacts of mild to severe hypoxia on human red blood cell (RBC)-nitric oxide synthase (NOS)-dependent NO production, protein S-nitrosylation and deformability.Ambient air oxygen concentration of 12 healthy subjects was step-wisely reduced from 20.95% to 16.21%, 12.35%, 10% and back to 20.95%. Additional in vitro experiments involved purging of blood (±sodium nitrite) with gas mixtures corresponding to in vivo intervention.Vital and hypoxia-associated parameters showed physiological adaptation to changing demands. Activation of RBC-NOS decreased with increasing hypoxia. RBC deformability, which is influenced by RBC-NOS activation, decreased under mild hypoxia, but surprisingly increased at severe hypoxia in vivo and in vitro. This was causatively induced by nitrite reduction to NO which increased S-nitrosylation of RBC α- and β-spectrins -a critical step to improve RBC deformability. The addition of sodium nitrite prevented decreases of RBC deformability under hypoxia by sustaining S-nitrosylation of spectrins suggesting compensatory mechanisms of non-RBC-NOS-produced NO.The results first time indicate a direct link between maintenance of RBC deformability under severe hypoxia by non-enzymatic NO production because RBC-NOS activation is reduced. These data improve our understanding of physiological mechanisms supporting adequate blood and, thus, oxygen supply to different tissues under severe hypoxia.
authors.affiliation: Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Germany.|The German Research Center of Elite Sport (momentum), German Sport University Cologne, Germany.
authors.forename: Marijke
authors.initials: M
authors.lastname: Grau
authors.affiliation: Department of Internal Medicine I (Cardiology, Angiology, Pneumology), Friedrich-Schiller University, Jena, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lauten
authors.affiliation: Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Hoeppener
authors.affiliation: Department of Internal Medicine I (Cardiology, Angiology, Pneumology), Friedrich-Schiller University, Jena, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Goebel
authors.affiliation: Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Brenig
authors.affiliation: Department of Internal Medicine I (Cardiology, Angiology, Pneumology), Friedrich-Schiller University, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jung
authors.affiliation: Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Germany.|The German Research Center of Elite Sport (momentum), German Sport University Cologne, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.affiliation: Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Germany.|The German Research Center of Elite Sport (momentum), German Sport University Cologne, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Suhr
mesh_terms: D000328:Adult; D015687:Cell Hypoxia; D004907:Erythrocyte Deformability / Q000502:physiology; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: Humans; nitric oxide; normobaric hypoxia; red blood cell deformability; red blood cell-nitric oxide synthase; red blood cells