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Alveolar hypoxia-induced systemic inflammation: what low PO(2) does and does not do
Norberto C Gonzalez1, John G Wood
1Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. ngonzale@kumc.edu
Advances in Experimental Medicine and Biology
|March 6, 2010
Summary
Breathing low oxygen (alveolar hypoxia) causes rapid microvascular inflammation in rodents. This response, involving mast cells and the renin-angiotensin system, resolves with acclimatization, suggesting endothelial adaptation to hypoxia.
Area of Science:
- Physiology
- Pathology
- Microcirculation
Background:
- Alveolar hypoxia (AH) occurs in lung diseases like COPD and during rapid altitude ascent.
- Mechanisms of altitude illness and systemic inflammation in COPD are unclear.
- Systemic inflammation is a potential contributor to hypoxia-related illnesses.
Purpose of the Study:
- To investigate the microvascular inflammatory response to acute alveolar hypoxia.
- To elucidate the cellular and molecular mechanisms driving hypoxia-induced inflammation.
- To explore the process of vascular acclimatization to sustained hypoxia.
Main Methods:
- Induction of AH by breathing 10% O(2) in rats and mice.
- Direct observation of microvascular inflammation in mesenteric, skeletal muscle, and pial circulations.
- Assessment of mast cell degranulation, reactive oxygen species, nitric oxide, leukocyte adherence, and albumin extravasation.
Main Results:
- AH rapidly induced widespread microvascular inflammation within minutes.
- Inflammation involved mast cell degranulation, increased reactive oxygen species, and reduced nitric oxide.
- Sustained hypoxia led to resolution of inflammation, indicating vascular acclimatization.
- Evidence suggests alveolar macrophages release an intermediary activating mast cells.
Conclusions:
- Acute alveolar hypoxia triggers a rapid, widespread microvascular inflammatory cascade.
- The renin-angiotensin system and NADPH oxidase are key mediators of this response.
- Vascular endothelium can acclimatize to hypoxia, resolving inflammation over time.
- An alveolar macrophage-derived factor may initiate the inflammatory response to hypoxia.
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