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Systemic hypoxia increases leukocyte emigration and vascular permeability in conscious rats

Departments of 1  Molecular and Integrative Physiology and 2  Pediatrics, University of Kansas Medical Center, Kansas City, Kansas 66160 We recently observed that acute systemic hypoxia produces rapid increases in leukocyte adherence in the mesenteric microcirculation of the anesthetized rat Wood JG...

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Published in:Journal of applied physiology (1985) 2000-10, Vol.89 (4), p.1561-1568
Main Authors: Wood, John G, Johnson, Jennifer S, Mattioli, Leone F, Gonzalez, Norberto C
Format: Article
Language:English
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Summary:Departments of 1  Molecular and Integrative Physiology and 2  Pediatrics, University of Kansas Medical Center, Kansas City, Kansas 66160 We recently observed that acute systemic hypoxia produces rapid increases in leukocyte adherence in the mesenteric microcirculation of the anesthetized rat Wood JG, Johnson JS, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 1734-1740, 1999; Wood JG, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 873-881, 1999. Hypoxia-induced leukocyte adherence is associated with an increase in reactive oxygen species (ROS) generation and is attenuated by antioxidants or interventions that increase tissue levels of nitric oxide (NO). These results suggest that the acute effects of hypoxia on leukocyte-endothelial interactions are caused by a change in the ROS-NO balance. The present experiments were designed to extend our observations of the initial microcirculatory response to hypoxia; specifically, we wanted to determine whether the response to systemic hypoxia involves increased microvascular permeability and leukocyte emigration and whether ROS generation and decreased NO levels contribute to these responses. At this time, there is conflicting evidence, from in vitro studies, regarding the effect of hypoxia on these indexes of vascular function. Our studies were carried out in the physiological setting of the conscious animal, in which a prolonged hypoxic exposure is possible without the adverse effects that may develop under anesthesia. The central observation of these studies is that conscious animals exposed for 4 h to environmental hypoxia show increased microvascular permeability and emigration of leukocytes into the extravascular space of the mesenteric circulation. Furthermore, these events are dependent on increased ROS generation and, possibly, a subsequent decrease in tissue NO levels during systemic hypoxia. Our results show that systemic hypoxia profoundly affects vascular endothelial function through changes in the ROS-NO balance in the conscious animal. mesenteric microcirculation; endothelial cells; venules; nitric oxide donor; leukocyte-endothelial adhesive interactions
ISSN:8750-7587
1522-1601
DOI:10.1152/jappl.2000.89.4.1561