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Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation
Jack H Crawford1, T Scott Isbell, Zhi Huang
1Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, 35294, USA.
Blood
|October 1, 2005
Summary
Hypoxic red blood cells release nitric oxide (NO) and ATP, causing vasodilation. Hemoglobin acts as a nitrite reductase, linking oxygen sensing to increased blood flow.
Area of Science:
- Physiology
- Biochemistry
Background:
- Local vasodilation ensures oxygen delivery during metabolic stress.
- Red blood cells (RBCs), specifically hemoglobin, are identified as hypoxic sensors.
Purpose of the Study:
- Investigate mechanisms of hypoxic vasodilation.
- Explore roles of ATP, S-nitrosohemoglobin, and nitrite.
- Determine hemoglobin's function in oxygen sensing and NO production.
Main Methods:
- Assessed NO production and cGMP levels.
- Measured mitochondrial respiration.
- Utilized NO scavenger C-PTIO.
- Investigated hemoglobin's nitrite reductase activity at varying oxygenation levels.
- Examined effects of beta93cys residue mutation on hemoglobin function.
Main Results:
- Hypoxic RBCs mediate vasodilation via nitrite reduction to nitric oxide (NO) and ATP release.
- NO dependence confirmed by NO gas formation, cGMP stimulation, and inhibited mitochondrial respiration.
- Hemoglobin's nitrite reductase activity peaks at 50% oxygenation (P(50)), coinciding with vasodilation onset.
- Beta93cys mutation enhances nitrite reductase activity and vasodilation.
Conclusions:
- RBC hemoglobin functions as an allosterically and redox-regulated nitrite reductase.
- This enzyme activity links hypoxia sensing to NO-dependent vasodilation.
- Hemoglobin's oxygen-sensing mechanism is coupled to nitrite reduction and increased blood flow.