Abstract
Background: Acute mountain sickness (AMS) strikes people who travel too quickly to high altitude, outstripping their ability to acclimatize. Individual susceptibility to AMS remains unpredictable. The aim of study was to investigate the neuroendocrine mechanisms regulation of corticotropin-releasing hormone (CRH) and associated with AMS. Methods: Volunteers performed exercise by cycling or by running, and the other was assigned to ascend from low to high altitude. CRH and cortisol levels were tested. AMS questionnaires were answered by volunteers. Rats were exposed in a hypobaric chamber for altitude hypoxia. CRH, Crhr1mRNA, and corticosterone levels were measured. LDH and O2 saturation were evaluated. Results: In rats, hypobaric hypoxia resulted in increased CRH release and mRNA expression in the paraventricular nucleus (PVN). Hypobaric hypoxia also upregulated Crhr1mRNA in the pituitary and PVN in a hypoxia exposure-dependent manner, along with activation of apoptotic gene mRNA and neuronal apoptosis in cortex. These effects were associated with activation of CRHR1. Hypoxia-enhanced plasma CRH levels were negatively correlated with brain CRH level but positively with plasma corticosterone in rats. In humans, exercise at low altitude increased CRH and cortisol levels in both plasma and saliva. The increased levels in plasma correlated with increased salivary CRH. Significantly, lowlanders with high plasma CRH at low altitude developed AMS after rapid ascent to the Tibet plateau. At high altitude, lowlanders with high AMS scores had high salivary and plasma CRH levels. Conclusions: Hypobaric hypoxia is associated with high plasma CRH in rats. In humans, strong activation of CRH and CRHR1 is positively linked to AMS. CRH levels in saliva or plasma appear to predict individual responses to hypoxia.