Nitric oxide (NO) may act as either a pro-oxidant or an antioxidant in biological systems. Previous work has found inhalation of NO improved survival in a high altitude rat model. NO donor isosorbide mononitrate derivants might have a protective effect against hypoxia. We synthesized a series of isosorbide mononitrate derivant compounds to test their anti-hypoxia activities. Normobaric hypoxia and hypobaric hypoxia models were used to study the protective role of NO donor in mice. The results showed isosorbide mononitrate derivants had protective effects in hypoxia mice. Among those compounds, acetyl ferulic isosorbide mononitrate (AFIM) was the most effective. It prolonged the survival time during the normobaric hypoxia test. It decreased malondialdehyde (MDA) and H 2 O 2 in hypobaric hypoxia mice. The antioxidase activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) remained in normal ranges in the AFIM group. As a sign of mitochondrial dysfunction, the activities of ATPase were down regulated in mice under hypobaric hypoxia conditions. AFIM also protected ATPase activities. The protective effects of AFIM might come from a sustained NO supply and the release of acetyl ferulic acid with anti-oxidant activity.Key words altitude; hypoxia; nitric oxide; acetyl ferulic isosorbide mononitrate More than 140 M persons lives at above 2500 m (the conventional definition of high altitude as that where arterial O 2 saturation (SaO 2 ) measurably begins to fall).1) Barometric pressure falls with increasing altitude and consequently there is a reduction in the partial pressure of oxygen resulting in a hypoxic challenge to any individual ascending to altitude. With the ever increasing number of people ascending to high altitudes, medicines to deal with potential problems are becoming increasingly relevant to non-specialists, including general practitioners.A spectrum of high altitude illnesses can occur when the hypoxic stress outstrips the subject's ability to acclimatize. Acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) strike people who travel too fast to high altitudes that lie beyond their current level of acclimatization.
2)AMS is a condition affecting otherwise healthy individuals on going rapidly to altitude. A spectrum of symptoms related to acute mountain sickness may develop at altitudes below 3000 m: commonly reported symptoms are nausea, vomiting, headache, dizziness, fatigue, and sleep disturbance.
3)Acute hypoxia induces pulmonary vascular permeability and contributes to forms of noncardiogenic pulmonary edema such as high altitude pulmonary edema and acute respiratory distress syndrome.4,5) AMS can sharply limit recreation and work at high altitude, especially in the first few days following arrival at a new, higher altitude, and if AMS worsens and HACE develops, the risk of fatality is significant. 6) Although slow ascent to altitude remained the most important measure to prevent acute mountain sickness, evidence from the literature on high altitude...