title: Alternative hematological and vascular adaptive responses to high-altitude hypoxia in East African highlanders.
abstract: Elevation of hemoglobin concentration, a common adaptive response to high-altitude hypoxia, occurs among Oromo but is dampened among Amhara highlanders of East Africa. We hypothesized that Amhara highlanders offset their smaller hemoglobin response with a vascular response. We tested this by comparing Amhara and Oromo highlanders at 3,700 and 4,000 m to their lowland counterparts at 1,200 and 1,700 m. To evaluate vascular responses, we assessed urinary levels of nitrate (NO3-) as a readout of production of the vasodilator nitric oxide and its downstream signal transducer cyclic guanosine monophosphate (cGMP), along with diastolic blood pressure as an indicator of vasomotor tone. To evaluate hematological responses, we measured hemoglobin and percent oxygen saturation of hemoglobin. Amhara highlanders, but not Oromo, had higher NO3-and cGMP compared with their lowland counterparts. NO3-directly correlated with cGMP (Amhara R2= 0.25, P < 0.0001; Oromo R2= 0.30, P < 0.0001). Consistent with higher levels of NO3-and cGMP, diastolic blood pressure was lower in Amhara highlanders. Both highland samples had apparent left shift in oxyhemoglobin saturation characteristics and maintained total oxyhemoglobin content similar to their lowland counterparts. However, deoxyhemoglobin levels were significantly higher, much more so among Oromo than Amhara. In conclusion, the Amhara balance minimally elevated hemoglobin with vasodilatory response to environmental hypoxia, whereas Oromo rely mainly on elevated hemoglobin response. These results point to different combinations of adaptive responses in genetically similar East African highlanders.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.|Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Hoi I
authors.initials: HI
authors.lastname: Cheong
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Janocha
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Monocello
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Adrianna C
authors.initials: AC
authors.lastname: Garchar
authors.affiliation: Addis Ababa University Faculty of Medicine, Addis Ababa, Ethiopia; and.
authors.forename: Amha
authors.initials: A
authors.lastname: Gebremedhin
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.|Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.affiliation: Department of Anthropology, Case Western Reserve University, Cleveland, Ohio cmb2@case.edu.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Beall
mesh_terms: D000222:Adaptation, Physiological; D000351:Africa, Eastern; D000531:Altitude; D000532:Altitude Sickness / Q000097:blood* / Q000150:complications / Q000503:physiopathology / Q000652:urine; D001794:Blood Pressure; D001808:Blood Vessels / Q000503:physiopathology*; D006152:Cyclic GMP / Q000378:metabolism; D003710:Demography; D003971:Diastole; D005006:Ethnicity; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000150:complications / Q000503:physiopathology / Q000652:urine; D009566:Nitrates / Q000652:urine; D010108:Oxyhemoglobins / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D009566:Nitrates; D010108:Oxyhemoglobins; C100003:deoxyhemoglobin; D006152:Cyclic GMP
keywords: Amhara; Oromo; adaptation; cyclic guanosine monophosphate; deoxyhemoglobin; high altitude; hypoxia; nitric oxide; oxyhemoglobin