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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/H1096    most recent 01037.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhou, X. Articles by He, P. Search for Related Content PubMed PubMed Citation Articles by Zhou, X. Articles by He, P.

Calcium influx-dependent differential actions of superoxide and hydrogen peroxide on microvessel permeability

Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, West Virginia

Submitted 28 September 2008 ; accepted in final form 31 January 2009

Our previous study demonstrated that reactive oxygen species (ROS) released from activated blood cells contribute significantly to the increased microvessel permeability during inflammation. This study aims to define the individual roles of hydrogen peroxide (H₂O₂) and superoxide in ROS-induced increases in permeability and endothelial intracellular Ca²⁺ concentration ([Ca²⁺]_i) in individually perfused rat mesenteric venules. Microvessel permeability was determined by measuring hydraulic conductivity (L_p). Endothelial [Ca²⁺]_i was measured in fura-2 AM-loaded microvessels. Perfusing microvessels with superoxide generated by hypoxanthine and xanthine oxidase (HX/XO) induced immediate and transient increases in L_p. The mean peak value, which occurred within 5 min of HX/XO exposure, was 4.3 ± 0.6 times that of the control. In contrast, the perfusion of H₂O₂ (100 and 500 µM) caused no immediate increases in L_p. A significant L_p increase, 3.6 ± 0.6 times the control value, occurred 30 min after the perfusion of H₂O₂ at 500 µM. The perfusion of H₂O₂ at 100 or 500 µM for 1 h increased L_p to 6.6 ± 0.9 and 11.3 ± 3.6 times the control value, respectively. The increased endothelial [Ca²⁺]_i in HX/XO or H₂O₂ perfused vessels was correlated with the time course of the increases in L_p. Inhibiting Ca²⁺ influx by LaCl₃ prevented the permeability increase induced by HX/XO or H₂O₂. These results demonstrated differential actions of superoxide and H₂O₂ on microvessel permeability and endothelial [Ca²⁺]_i. Superoxide-induced permeability increases were immediate and transient, whereas H₂O₂-induced permeability increases were progressive, demonstrating concentration and time dependence. Ca²⁺ influx plays an essential role in both superoxide and H₂O₂-induced permeability increases.

hydraulic conductivity; reactive oxygen species; endothelial calcium imaging