The Fetal Llama versus the Fetal Sheep: Different Strategies to Withstand Hypoxia

Abstract

The pregnant llama (Lama glama) has walked for millions of years through the thin oxygen trail of the Andean altiplano. We hypothesize that a pool of genes has been selected in the llama that express efficient mechanisms to withstand this low-oxygen milieu. The llama fetus responds to acute hypoxia with an intense peripheral vasoconstriction that is not affected by bilateral section of the carotid sinus nerves. Moreover, the increase in fetal plasma concentrations of vasoconstrictor hormones, such as catecholamines, neuropeptide Y, and vasopressin, is much greater in the llama than in the sheep fetus. Furthermore, treatment of fetal llamas with an alpha-adrenergic antagonist abolished the peripheral vasoconstriction and resulted in fetal cardiovascular collapse and death during acute hypoxia, suggesting an indispensable upregulation of alpha-adrenergic mechanisms in this high altitude species. Local endothelial factors such as nitric oxide (NO) also play a key role in the regulation of fetal adrenal blood flow and in the adrenal secretion of catecholamines and cortisol. Interestingly, in contrast to the human or sheep fetus, the llama fetus showed a small increase in brain blood flow during acute hypoxia, with no increase in oxygen extraction across the brain, and thereby a decrease in brain oxygen consumption. These results suggest that the llama fetus responds to acute hypoxia with hypometabolism. How this reduction in metabolism is produced and how the cells are preserved during this condition remain to be elucidated.

Hypotension in the chronically hypoxic chicken embryo is related to the β-adrenergic response of chorioallantoic and femoral arteries and not to bradycardia

“…Despite an assumingly lower NOmediated vasorelaxation in the chronic hypoxic chicken embryo due to impaired endothelial function, we still observe a hypotensive response to chronic hypoxia. We have previously shown that the CAM vasculature is not innervated, i.e., is not subject to cholinergic stimulation of NO release (in fact, exogenous ACh does not relax, but constricts, CA arteries) (27). Additionally, we report here that the femoral arteries from hypoxic chicken embryos show an increased sensitivity to ␤AR-mediated relaxation.…”

“…1), yet hypotension remained. In the absence of a chemoreflex, cardiovascular function in the chicken embryo is mainly maintained through adrenergic pathways stimulated by catecholamines of adrenomedullary rather than sympathetic origin (11), which, in turn, could elevate heart rate as shown in the chronically hypoxic sheep fetus (14,27). Circulating norepinephrine levels are increased in E19 chickens (Fig.…”

“…This reflex is instrumental in the redistribution of cardiac output (CO) to the heart, brain, and adrenals, while blood is diverted away from the liver and kidneys (14,32). The initial hypoxic bradycardia is transient, and HR returns to baseline values during a more prolonged hypoxic period, likely due to the increase of humoral factors, such as catecholamines or vasopressin (14,27).…”

Long-term hypoxia increases calcium affinity of BK channels in ovine fetal and adult cerebral artery smooth muscle

“…During high-altitude LTH, the CBF in adult humans (23,60) and sheep (34,63) returns to normal following a period of transitional increased blood flow, as compiled by Brugniaux et al (8). The ovine near-term fetus diverts an increased fraction of total cardiac output to the brain, when subjected to hypoxia during gestation.…”

A proposed classification of environmental adaptation: the example of high altitude

“…Some chickens found on the Peruvian Altiplano show a mutant hemoglobin with a high affinity for O 2 when compared to their sea level cousins (Mejia et al 1994). Adaptation can also be seen at the embryo level: the permeability of the egg shell of some high altitude birds is higher than the similar species living at sea level (Leon-Velarde et al 1997), cerebral blood flow of the llama's fetus does not increase in hypoxia, as opposed to what happens in sea level sheep (Llanos et al 2003). Further investigations in humans and animal species adapted to high altitude will be necessary to better understand how living organisms cope with hypoxia, using so various strategies.…”