Dynamic cerebral autoregulation is impaired in acute mountain sickness; focus on redox regulation of systemic nitric oxide bioavailability [Abstract]

PURPOSE: The present study examined whether a decrease in systemic nitric oxide (NO) bioavailability subsequent to increased oxidative stress in hypoxia would impair cerebral autoregulation (CA), elevate intracranial pressure (ICP) and increase susceptibility to acute mountain sickness (AMS). METHODS: Arterial blood pressure (ABP-photoplethysmography) and middle cerebral artery velocity (MCAv-transcranial Doppler) were measured in 18 males at rest in normoxia and following 6h passive exposure to normobaric hypoxia (12%O2). A dynamic rate of CA was determined by the rate of regulation (RoR) and transfer function (TF) analysis (0.07-0.20Hz) during a transient period of hypotension (leg-cuff technique). Venous samples (not corrected for volume shifts) were assayed for total nitric oxide (NOx) via ozone-based chemiluminescence and the ascorbate radical (A·-) by electron paramagnetic resonance spectroscopy. Clinical AMS (moderate to severe) was diagnozed as a Lake Louise score of <=5 points and Environmental Symptoms Questionnaire cerebral symptoms score <=0.7 points. RESULTS: Nine subjects were diagnozed with AMS (AMS+) and were characterized by a greater increase in plasma A·- during hypoxia (AMS+: +461 ± 215 arbitrary units (AU)[square root]Gauss (G) vs. AMS-: +30 ± 237 AU[square root]G, P 0.05). The AMS+ subgroup experienced a greater reduction in RoR and increase in TF gain (P< 0.05 vs. AMS-) which was consistently related to the increase in symptom scores (r= -0.66 to -0.70, P< 0.05). This translated into a greater increase in eICP (AMS: +8.5 ± 9.1 vs. AMS-: -6.5 ± 9.5 mmHg, P < 0.05). CONCLUSION: These findings identify oxidative stress, impaired CA and intracranial hypertension as potential risk factors for AMS whereas systemic NO metabolism appears unimportant