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 (NO) 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 NO and cGMP compared with their lowland counterparts. NO directly correlated with cGMP (Amhara R = 0.25, P < 0.0001; Oromo R = 0.30, P < 0.0001). Consistent with higher levels of NO 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.

The increase in hemoglobin concentration with altitude varies among human populations

“…Refs : 1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 19; 20; 21; – 22; – 23; – 24; 25; 26; – 27; – 28; 29; 30; – 31; – 32; 33; 34; – 35; 36; – 37; – 38; 39; – – 40; – 41; 42; 43;…”

The impact of hypoxaemia on vascular function in lowlanders and high altitude indigenous populations

“…; Cheong et al . ), suggesting the Oromo present a similar response to high altitude as lowlanders. An adaptive vascular phenotype has been suggested in Amhara highlanders, based upon urinary levels of nitrate and cyclic guanosine monophosphate (Cheong et al .…”

“…An adaptive vascular phenotype has been suggested in Amhara highlanders, based upon urinary levels of nitrate and cyclic guanosine monophosphate (Cheong et al . ); however, these are indirect and non‐specific measures and no studies of the systemic vasculature have been conducted in this population.…”

Blood pressure at high altitude: physiology and clinical implications

“…A clear increase of 24-hour, countries and between urban and rural areas, climatic effects, genetic adaptations, and epigenetic mechanisms. 24 Nighttime BP merits a special mention in this regard. It is still not clear why an increase in BP may be more pronounced during the night, but there are several hypotheses.…”