Transcerebral exchange kinetics of nitrite and calcitonin gene-related peptide in acute mountain sickness: evidence against trigeminovascular activation?

Abstract

High-altitude headache is the primary symptom associated with acute mountain sickness, which may be caused by nitric oxide-mediated activation of the trigeminovascular system. Therefore, the present study examined the effects of inspiratory hypoxia on the transcerebral exchange kinetics of the vasoactive molecules, nitrite (NO(2)(*)), and calcitonin gene-related peptide (CGRP). Ten males were examined in normoxia and after 9-hour exposure to hypoxia (12.9% O(2)). Global cerebral blood flow was measured by the Kety-Schmidt technique with paired samples obtained from the radial artery and jugular venous bulb. Plasma CGRP and NO(2)(*) were analyzed via radioimmunoassay and ozone-based chemiluminescence. Net cerebral exchange was calculated by the Fick principle and acute mountain sickness/headache scores assessed via clinically validated questionnaires. Hypoxia increased cerebral blood flow with a corresponding increase in acute mountain sickness and headache scores (P<0.05 vs normoxia). Hypoxia blunted the cerebral uptake of NO(2)(*), whereas CGRP exchange remained unaltered. No relationships were observed between the change (hypoxia-normoxia) in cerebral NO(2)(*) or CGRP exchange and acute mountain sickness/headache scores (P>0.05). These findings argue against sustained trigeminovascular system activation as a significant event in acute mountain sickness.