In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 132, No. suppl_3 ( 2015-11-10)
Abstract:
Rationale: To better understand human adaptation to hypoxia, we took advantage of one of the nature’s experiments at high altitude (HA) and studied Ethiopians, a human population that is well adapted to HA hypoxia. Using whole genome sequencing, we identified EDNRB, endothelin receptor type B, as a candidate gene involved in HA adaptation. Objective: We hypothesize that EDNRB plays a critical role in hypoxia and therefore in HA adaptation through regulating cardiac function. Methods and Results: We generated EdnrB knockout mice and found that the EdnrB-/+ mice were phenotypically normal. However, when treated with lower levels of oxygen (O2), EdnrB-/+ mice tolerated various levels of hypoxia, sustaining ejection fraction, cardiac contractility and cardiac output to even 5% O2. Blood lactate levels remained low and O2 delivery to vital organs was significantly higher in EdnrB-/+. Tissues sensitive to hypoxia, such as brain, heart and kidney, were less hypoxic indicating better peripheral perfusion. Conclusion: These data indicate that a lower level of EDNRB significantly improves cardiac performance and tissue perfusion under various levels of hypoxia. Our findings in EdnrB-/+ mice provide strong evidence that 1) EDNRB plays a key role in the adaptation to HA whereby a lower activation of EDNRB leads to a better cardiac performance under hypoxic conditions and 2) HA adaptation studies can be pertinent to understanding responses to acute hypoxia at sea level.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.132.suppl_3.16038
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2015
detail.hit.zdb_id:
1466401-X
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