Reduction of alveolar PO2 (alveolar hypoxia, AH) may occur in pulmonary diseases such as chronic obstructive pulmonary disease (COPD), or in healthy individuals ascending to altitude. Altitude illnesses may develop in non-acclimatized persons who ascend rapidly. The mechanisms underlying these illnesses are not well understood, and systemic inflammation has been suggested as a possible contributor. Similarly, there is evidence of systemic inflammation in the systemic alterations present in COPD patients, although its role as a causative factor is not clear.
We have observed that AH, induced by breathing 10% O2 produces a rapid (minutes) and widespread micro vascular inflammation in rats and mice. This inflammation has been observed directly in the mesenteric, skeletal muscle, and pial microcirculations. The inflammation is characterized by mast cell degranulation, generation of reactive O2 species, reduced nitric oxide levels, increased leukocyte-endothelial adherence in post-capillary venules, and extravasation of albumin. Activated mast cells stimulate the renin-angiotensin system (RAS) which leads to the inflammatory response via activation of NADPH oxidase. If the animals remain in hypoxia for several days, the inflammation resolves and exposure to lower PO2 does not elicit further inflammation, suggesting that the vascular endothelium has “acclimatized” to hypoxia.
Recent experiments in cremaster microcirculation suggest that the initial trigger of the inflammation is not the reduced tissue PO2, but rather an intermediary re-leased by alveolar macrophages into the circulation. The putative intermediary ac-tivates mast cells, which, in turn, stimulate the local renin-angiotensin system and induce inflammation.
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