Systemic hypoxia promotes leukocyte-endothelial adherence via reactive oxidant generation

• Published in: Journal of applied physiology (1985) 1999-11, Vol.87 (5), p.1734-1740
• Main Authors: Wood, John G, Johnson, Jennifer S, Mattioli, Leone F, Gonzalez, Norberto C
• Format: Article
• Language: English
• Subjects: Anatomy & physiology; Animals; Antioxidants; Antioxidants - pharmacology; Biological and medical sciences; Blood vessels and receptors; Catalase - pharmacology; Cell Adhesion - drug effects; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Hypoxia - physiopathology; Leukocytes; Leukocytes - drug effects; Leukocytes - physiology; Male; Microcirculation - drug effects; Microcirculation - physiology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Reactive Oxygen Species - physiology; Rhodamines - pharmacology; Rodents; Splanchnic Circulation - drug effects; Splanchnic Circulation - physiology; Superoxide Dismutase - pharmacology; Thioctic Acid - pharmacology; Vertebrates: cardiovascular system
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.1999.87.5.1734

Departments of 1  Molecular and Integrative Physiology and 2  Pediatrics, University of Kansas Medical Center, Kansas City, Kansas 66160 We recently demonstrated that systemic hypoxia during reduced inspired P O 2 produces a rapid increase in leukocyte adherence to rat mesenteric venules. Evidence suggests that the mechanism of this response involves decreased nitric oxide (NO) levels. One possible pathway for NO depletion could involve increased reactive oxygen species (ROS) generation resulting in inactivation of NO. The overall goal of the present study was to examine the role of ROS in promoting leukocyte-endothelial adherence during systemic hypoxia. Experiments were designed to 1 ) evaluate changes in ROS generation in the mesenteric microcirculation during systemic hypoxia, 2 ) determine how the ROS signal changes when P O 2 levels return to normal after a period of systemic hypoxia, 3 ) assess the effect of antioxidants on ROS generation during hypoxia, and 4 ) utilize antioxidants to examine the functional relationship between ROS generation and leukocyte adherence during hypoxia. The major findings from this study are that systemic hypoxia increases ROS generation within the mesenteric microcirculation and that antioxidants prevent the increase in leukocyte-endothelial adhesive interactions observed in hypoxia. antioxidants; superoxide dismutase/catalase; lipoic acid; dihydrorhodamine 123; nitric oxide; acute hypoxia; mesenteric microcirculation; reactive oxygen species