| First Author | Keller TCS 4th | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 6405 |
| PubMed ID | 36302779 | Mgi Jnum | J:346559 |
| Mgi Id | MGI:7379598 | Doi | 10.1038/s41467-022-34154-3 |
| Citation | Keller TCS 4th, et al. (2022) Endothelial alpha globin is a nitrite reductase. Nat Commun 13(1):6405 |
| abstractText | 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 Hba1Delta/Delta) and another with an alpha globin allele mutated to prevent alpha globin's inhibitory interaction with endothelial nitric oxide synthase (Hba1WT/Delta36-39). The EC Hba1Delta/Delta mice had significantly decreased exercise capacity and intracellular nitrite consumption in hypoxic conditions, an effect absent in Hba1WT/Delta36-39 mice. Hypoxia-induced vasodilation is significantly decreased in arteries from EC Hba1Delta/Delta, but not Hba1WT/Delta36-39 mice. Hypoxia also does not lower blood pressure in EC Hba1Delta/Delta 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. |
