Endothelial alpha globin is a nitrite reductase

• DOI: 10.1038/s41467-022-34154-3
• Publication Date: 2022-10-27T14:05:52Z
• Authors: T. C. Stevenson K...; Christophe Lechauve; Alexander S. Keller; Gilson Brás Brose...; Joshua T. Butcher; Henry R. Askew Page; Aditi Islam; Zhe Yin Tan; Leon J. DeLalio; Steven Brooks; Poonam Sharma; Kwangseok Hong; Wenhao Xu; Alessandra Simão ...; Claire A. Ruddiman; Angela K. Best; Edgar Macal; Daniel B. Kim-Sha...; George Christ; Zhen Yan; Miriam M. Cortese...; Karina Ricart; Rakesh Patel; Timothy P. Bender; Swapnil K. Sonkusare; Mitchell J. Weiss; Hans Ackerman; Linda Columbus; Brant E. Isakson
• Keywords: Hypoxia

Abstract 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 expressed endothelium also facilitates reduction proximal smooth muscle. Here, we create two mouse strains test this: an endothelial-specific globin knockout (EC Hba1Δ/Δ) another with allele mutated prevent globin’s inhibitory interaction endothelial synthase (Hba1WT/Δ36–39). The EC Hba1Δ/Δ mice had significantly decreased exercise capacity intracellular consumption hypoxic conditions, effect absent Hba1WT/Δ36–39 mice. Hypoxia-induced arteries from Hba1Δ/Δ, but not Hypoxia does lower blood pressure conclude presence resistance acts as a reductase providing local hypoxia.