Leukocyte-endothelial interactions in environmental hypoxia.
Hypoxia induced by reducing inspired PO2 (PIO2) to 70 Torr, promotes a rapid microvascular response characterized by increased leukocyte rolling and adherence to the venular endothelium, leukocyte emigration to the perivascular space and increased vascular permeability. This appears to be a generalized response since it is observed in venules of the mesentery, cremaster muscle and pial microcirculations. After three weeks of acclimatization to hypoxia (barometric pressure 380 Torr, PIO2 70 Torr), the initial microvascular response resolves and exposure to even lower PIO2 (50 Torr) fails to elicit a microvascular response. The initial response is accompanied by a reversible increase in the generation of reactive oxygen species (ROS) and is blocked by antioxidants and by interventions that increase the tissue levels of nitric oxide (NO). In contrast to ischemia/reperfusion, ROS levels increase during hypoxia and return towards pre-hypoxic values after return to normoxia. Acclimatization involves upregulation of inducible NO synthase (iNOS): inhibition of iNOS using two different antagonists results in increased leukocyte-endothelial interactions and increased ROS generation. The results suggest that hypoxia initially leads to an alteration of the ROS/NO balance which is eventually restored during the acclimatization process. This phenomenon may have relevance to the microcirculatory alterations associated with hypoxic exposure, including acute mountain sickness and high altitude pulmonary and cerebral edema.
Gonzalez
N C
NC
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, USA.
Wood
J G
JG
D000532:Altitude Sickness / Q000150:complications / Q000378:metabolism; D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D004777:Environment; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D009569:Nitric Oxide