Voluntary physical activity does not improve with attenuated vascular permeability in a model of acute mountain sickness

Acute mountain sickness (AMS) affects > 60% of individuals ascending to altitude, yet the etiology is unclear. Symptoms include lethargy, inactivity, headache, and in severe cases pulmonary or cerebral edema. Pulmonary and cerebral edema are characterized by leakage of fluid from the vascular space into pulmonary and cerebral tissues. Current treatments for AMS are targeted at vasodilation, enhancing fluid clearance, and increasing ventilation. HypothesisWe postulated that decreasing the vascular permeability that gives rise to pulmonary and cerebral edema would result in a return of physical activity (PA) to normoxic levels. MethodsAdult male SD rats were acclimated to voluntary PA for at least one wk using running wheels. Rats were then exposed to48 hrs of 14,000ft simulated altitude and treated with combinations of compounds to decrease vascular leak including endothelin receptor (ETr) antagonists, Nrf2 activators, carbonic anhydrase (CA) inhibitors, Ca++ channel blockers, and phosphodiesterase (PDE) i...