Oxidative stress in hypobaric hypoxia and influence on vessel-tone modifying mediators.

摘要: Increased pulmonary artery pressure is a well-known phenomenon of hypoxia and seen in patients with chronic diseases, also mountaineers on high altitude expedition. Different mediators are known to regulate vessel tone. However, exact mechanisms not fully understood multimodal process consisting whole panel supposed cause vasoconstriction. We hypothesized that increased hypoxemia associated an increase vasoconstrictive decrease vasodilatators leading net effect. Furthermore, we suggested oxidative stress being partly involved changement these parameters. Oxygen saturation (Sao2) clinical parameters were assessed 34 volunteers before during Swiss research expedition Mount Muztagh Ata (7549 m) Western China. Blood samples taken at four different sites up 6865 m. A mass spectrometry-based targeted metabolomic platform was used detect multiple parameters, revealed functional impairment enzymes require oxidation-sensitive cofactors. Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 0.14 6265 m), indicating NO availability resulting less vasodilatative activity. Correspondingly, systemic found significant percentage methionine sulfoxide 6% under normoxic condition level 30% (p<0.001) camp 1 5533 (e.g., tryptophan, serotonin, peroxidation-sensitive lipids) found. During ascent m, altitude-dependent changes vessel-tone modifying excess metabolites could be demonstrated. These changes, as well highly stress, may predictive for acute mountain sickness score Sao2.