Abstract
People living in a high-altitude environment have distinct lifelong challenges. Adaptive mechanisms have allowed high-altitude residents to survive in a low-oxygen environment for thousands of years. The purpose of this review was to provide a brief review of the Ethiopian native highlanders' adaptive mechanisms to chronic hypoxia problems at high altitude. Traditionally, an elevated hemoglobin concentration has been considered as a hallmark of lifelong adaptation to high-altitude hypoxia, though this notion has been refuted recently as a result of the establishment of the alternative adaptive responses found in Amhara highlanders living in the Simien Mountains of northern Ethiopia. These populations did not have elevated hemoglobin (no erythrocytosis) but had normal hemoglobin saturation and arterial oxygen level, which alerts researchers to explore the possibility of the presence of an alternative adaptive mechanism. Contrary to this, Oromos living in the Bale Mountains of southern Ethiopia have elevated hemoglobin. The presence of increased nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in native Amhara highlanders suggests the possibility of adaptation via vasodilation, which would improve oxygen supply to metabolic tissues. Native Amhara highlanders showed no indications of chronic mountain sickness and had a higher pulmonary blood pressure without having a higher pulmonary vascular resistance. In addition, the cerebral circulation is sensitive to NO and carbon dioxide (CO(2)) but not to hypoxia, which would likely promote increased cerebral blood flow and increase oxygen delivery to the brain, making Ethiopian high-altitude natives better suited for survival at high altitudes. Further research is warranted to translate these background natural features of Ethiopian native highlanders to clinical applications.