Transcerebral Exchange Kinetics of Nitrite and Calcitonin Gene-Related Peptide in Acute Mountain Sickness Evidence Against Trigeminovascular Activation?

Background and Purpose-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 (NO2 center dot), and calcitonin gene-related peptide (CGRP). Methods-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 NO2 center dot 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. Results-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 NO2 center dot, whereas CGRP exchange remained unaltered. No relationships were observed between the change (hypoxia-normoxia) in cerebral NO2 center dot or CGRP exchange and acute mountain sickness/headache scores (P>0.05). Conclusion-These findings argue against sustained trigeminovascular system activation as a significant event in acute mountain sickness. (Stroke. 2009; 40: 2205-2208.)