Regulation of red blood cell deformability is independent of red blood cell-nitric oxide synthase under hypoxia

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2016

Erschienen:

2016

Enthalten in:

Zur Gesamtaufnahme - volume:63

Enthalten in:

Clinical hemorheology and microcirculation - 63(2016), 3 vom: 12. Sept., Seite 199-215

Sprache:

Englisch

Beteiligte Personen:

Grau, Marijke [VerfasserIn]
Lauten, Alexander [VerfasserIn]
Hoeppener, Steffen [VerfasserIn]
Goebel, Bjoern [VerfasserIn]
Brenig, Julian [VerfasserIn]
Jung, Christian [VerfasserIn]
Bloch, Wilhelm [VerfasserIn]
Suhr, Frank [VerfasserIn]

Links:

Volltext

Themen:

31C4KY9ESH
EC 1.14.13.39
Humans
Journal Article
Nitric Oxide
Nitric Oxide Synthase
Nitric oxide
Normobaric hypoxia
Red blood cell deformability
Red blood cell-nitric oxide synthase
Red blood cells

Anmerkungen:

Date Completed 16.02.2017

Date Revised 02.12.2018

published: Print

Citation Status MEDLINE

doi:

10.3233/CH-162044

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM257602941