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Roles of HIF‐1 on ventilatory, metabolic and mitochondrial cox responses to hypoxia in rats
Author(s) -
Demarest Maud,
Marcouiller François,
Ganouna Gauthier,
Soliz Jorge,
Joseph Vincent
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03482
Subject(s) - hypoxia (environmental) , respiration , hypoxic ventilatory response , medicine , respiratory system , endocrinology , cytochrome c oxidase , ventilation (architecture) , metabolism , biology , anaerobic exercise , chemistry , oxygen , mitochondrion , biochemistry , physiology , anatomy , mechanical engineering , organic chemistry , engineering
The lack of oxygen at high altitudes presents constraints for mammals. One of the mechanisms involved in the response to hypoxia is the stabilization of HIF‐1 (Hypoxia Inducible Factor 1) which contributes to ventilatory and metabolic responses, reduces mitochondrial respiration and stimulates anaerobic glycolysis. Upon acute hypoxia exposure, the expression of HIF‐1 reaches peak levels after a few hours of hypoxic exposure. In rats, however, the expression of HIF‐1 in hypoxia appears to be limited, as are the ventilatory and metabolic responses in comparison to other species better adapted to altitude. The purpose of this study is to better understand the interactions between hypoxia and HIF‐1 and to determine if there are other mechanisms possibly related to hypoxic responses. To this end, we measured ventilation and metabolic rate under resting conditions (whole body plethysmography) and mitochondrial respiration of the cerebral cortex and liver (oxygraphy) in adult male SD rats exposed in normoxia (21% O2 ‐ 6h), in hypoxia (10% O2 ‐ 6h), in normoxia after injection of a HIF‐1 stabilizer (deferoxamine; 100mg/kg), and in hypoxia after injection of a HIF‐1 inhibitor (2‐methoxyestradiol; 5mg/kg). Hypoxia reduces metabolism, increases minute ventilation and respiratory rate by 171 and 59% respectively and increases cytochrome c oxidase (COX) activity by an average of 72% in the cortex. Stabilization of HIF‐1 in normoxia doesn't result in any of these responses. However, inhibition of HIF‐1 in hypoxia decreases ventilatory responses by 30% for minute ventilation and 23% for respiratory rate and completely blocks the increase in COX activity. HIF‐1 would therefore be totally responsible for the IV complex responses observed in hypoxia, but would only be partially involved in the ventilatory response. There thus appears to be an interaction between HIF‐1 and other factors induced in hypoxia to establish ventilatory responses.