NO and hypoxia: Taking nitrate to new heights

Abstract

Residents of the Tibetan plateau appear to produce more nitric oxide (NO) compared to lowlanders as indicated by enhanced NO concentrations in exhaled breath and elevated levels of NO metabolites (incl. nitrite, nitrate and nitroso species) in their blood. This adaptation may help offset the consequences of life-long exposure to reduced atmospheric oxygen at high altitude by improving oxygen delivery and/or utilization and thus hypoxic tolerance. Recently, lowland participants of two independent research expeditions to Nepal have been demonstrated to also respond to environmental hypoxia with enhanced NO formation, suggesting this to be an integral part of human physiology that contributes to the process of acclimatization to reduced oxygen availability. Furthermore, dietary nitrate has been demonstrated to reduce the oxygen cost of exercise by improving mitochondrial efficiency at sea level and suggested to be sequentially reduced to nitrite and NO in hypoxia. This pathway could theoretically complement NOS-mediated l -arginine oxidation by providing an alternative source of NO under conditions of reduced oxygen availability. We hypothesized, therefore, that dietary nitrate administration may improve oxygen efficiency at high altitude, and this rationale has been tested in a randomized, double-blind field study carried out during summer 2010 at the Margherita Hut at 4,559 m ( Xtreme Alps ). This presentation will highlight some of the key results of this study and discuss their potential implications for the treatment of patients suffering from hypoxemia during critical illness.