Endothelial alpha globin is a nitrite reductase.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 10 2022
27 10 2022
Historique:
received:
28
02
2021
accepted:
04
10
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
1
11
2022
Statut:
epublish
Résumé
Resistance artery vasodilation in response to hypoxia is essential for matching tissue oxygen and demand. In hypoxia, erythrocytic hemoglobin tetramers produce nitric oxide through nitrite reduction. We hypothesized that the alpha subunit of hemoglobin expressed in endothelium also facilitates nitrite reduction proximal to smooth muscle. Here, we create two mouse strains to test this: an endothelial-specific alpha globin knockout (EC Hba1Δ/Δ) and another with an alpha globin allele mutated to prevent alpha globin's inhibitory interaction with endothelial nitric oxide synthase (Hba1WT/Δ36-39). The EC Hba1Δ/Δ mice had significantly decreased exercise capacity and intracellular nitrite consumption in hypoxic conditions, an effect absent in Hba1WT/Δ36-39 mice. Hypoxia-induced vasodilation is significantly decreased in arteries from EC Hba1Δ/Δ, but not Hba1WT/Δ36-39 mice. Hypoxia also does not lower blood pressure in EC Hba1Δ/Δ mice. We conclude the presence of alpha globin in resistance artery endothelium acts as a nitrite reductase providing local nitric oxide in response to hypoxia.
Identifiants
pubmed: 36302779
doi: 10.1038/s41467-022-34154-3
pii: 10.1038/s41467-022-34154-3
pmc: PMC9613979
doi:
Substances chimiques
Nitrite Reductases
EC 1.7.-
Nitric Oxide
31C4KY9ESH
Nitrites
0
alpha-Globins
0
Hemoglobins
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
6405Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR050429
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG077783
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG064121
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM131829
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL137112
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL120840
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR077440
Pays : United States
Informations de copyright
© 2022. The Author(s).
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