Membrane depolarization and NADPH oxidase activation in aortic endothelium during ischemia reflect altered mechanotransduction

We previously showed that "ischemia" (abrupt cessation of flow) leads to rapid membrane depolarization and increased generation of reactive oxygen species (ROS) in lung microvascular endothelial cells. This response is not associated with anoxia but, rather, reflects loss of normal shear s...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2005, Vol.57 (1), p.H336-H343
Main Authors: MATSUZAKI, Ikuo, CHATTERJEE, Shampa, DEBOLT, Kris, MANEVICH, Yefim, QUNWEI ZHANG, FISHER, Aron B
Format: Article
Language:English
Subjects:
Biological and medical sciences
Fluorescence
Fundamental and applied biological sciences. Psychology
Potassium
Pulmonary arteries
Signal transduction
Vertebrates: cardiovascular system
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Summary:We previously showed that "ischemia" (abrupt cessation of flow) leads to rapid membrane depolarization and increased generation of reactive oxygen species (ROS) in lung microvascular endothelial cells. This response is not associated with anoxia but, rather, reflects loss of normal shear stress. This study evaluated whether a similar response occurs in aortic endothelium. Plasma membrane potential and production of ROS were determined by fluorescence microscopy and cytochrome c reduction in flow-adapted rat or mouse aorta or monolayer cultures of rat aortic endothelial cells. Within 30 s after flow cessation, endothelial cells that had been flow adapted showed plasma membrane depolarization that was inhibited by pretreatment with cromakalim, an ATP-sensitive K+ (KATP) channel agonist. Flow cessation also led to ROS generation, which was inhibited by cromakalim and the flavoprotein inhibitor diphenyleneiodonium. Aortic endothelium from mice with "knockout" of the KATP channel (KIR6.2) showed a markedly attenuated change in membrane potential and ROS generation with flow cessation. In aortic endothelium from mice with knockout of NADPH oxidase (gp91phox), membrane depolarization was similar to that in wild-type mice but ROS generation was absent. Thus rat and mouse aortic endothelial cells respond to abrupt flow cessation by KATP channel-mediated membrane depolarization followed by NADPH oxidase-mediated ROS generation, possibly representing a cell-signaling response to altered mechanotransduction. [PUBLICATION ABSTRACT]
ISSN:0363-6135
1522-1539