HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/1/H336    most recent 00025.2004v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Matsuzaki, I. Articles by Fisher, A. B. Search for Related Content PubMed PubMed Citation Articles by Matsuzaki, I. Articles by Fisher, A. B.

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

Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania

Submitted 12 January 2004 ; accepted in final form 24 August 2004

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⁺ (K_ATP) 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 K_ATP channel (K_IR6.2) showed a markedly attenuated change in membrane potential and ROS generation with flow cessation. In aortic endothelium from mice with knockout of NADPH oxidase (gp91^phox), 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 K_ATP channel-mediated membrane depolarization followed by NADPH oxidase-mediated ROS generation, possibly representing a cell-signaling response to altered mechanotransduction.

ATP-sensitive potassium channels; K_IR6.2; gp91^phox; fluorescence microscopy; flow adaptation

This article has been cited by other articles:

				S. Bertuglia Intermittent hypoxia modulates nitric oxide-dependent vasodilation and capillary perfusion during ischemia-reperfusion-induced damage Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1914 - H1922. [Abstract] [Full Text] [PDF]

				J. C. Lee, F. Bhora, J. Sun, G. Cheng, E. Arguiri, C. C. Solomides, S. Chatterjee, and M. Christofidou-Solomidou Dietary flaxseed enhances antioxidant defenses and is protective in a mouse model of lung ischemia-reperfusion injury Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L255 - L265. [Abstract] [Full Text] [PDF]

				T. Kahles, P. Luedike, M. Endres, H.-J. Galla, H. Steinmetz, R. Busse, T. Neumann-Haefelin, and R. P. Brandes NADPH Oxidase Plays a Central Role in Blood-Brain Barrier Damage in Experimental Stroke Stroke, November 1, 2007; 38(11): 3000 - 3006. [Abstract] [Full Text] [PDF]

				S. Chatterjee, S. Baeter, and J. Bhattacharya Endothelial and epithelial signaling in the lung Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L517 - L519. [Abstract] [Full Text] [PDF]

				N. J. Hong and J. L. Garvin Flow increases superoxide production by NADPH oxidase via activation of Na-K-2Cl cotransport and mechanical stress in thick ascending limbs Am J Physiol Renal Physiol, March 1, 2007; 292(3): F993 - F998. [Abstract] [Full Text] [PDF]

				N. Duerrschmidt, C. Stielow, G. Muller, P. J. Pagano, and H. Morawietz NO-mediated regulation of NAD(P)H oxidase by laminar shear stress in human endothelial cells J. Physiol., October 15, 2006; 576(2): 557 - 567. [Abstract] [Full Text] [PDF]

				M. Oelze, A. Warnholtz, J. Faulhaber, P. Wenzel, A. L. Kleschyov, M. Coldewey, U. Hink, O. Pongs, I. Fleming, S. Wassmann, et al. NADPH Oxidase Accounts for Enhanced Superoxide Production and Impaired Endothelium-Dependent Smooth Muscle Relaxation in BK{beta}1-/- Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1753 - 1759. [Abstract] [Full Text] [PDF]

				Y. Fang, E. R. Mohler III, E. Hsieh, H. Osman, S. M. Hashemi, P. F. Davies, G. H. Rothblat, R. L. Wilensky, and I. Levitan Hypercholesterolemia Suppresses Inwardly Rectifying K+ Channels in Aortic Endothelium In Vitro and In Vivo Circ. Res., April 28, 2006; 98(8): 1064 - 1071. [Abstract] [Full Text] [PDF]

				H. Cai A new mechanism for flow-mediated vasoprotection? Focus on "Lung endothelial cell proliferation with decreased shear stress is mediated by reactive oxygen species" Am J Physiol Cell Physiol, January 1, 2006; 290(1): C35 - C36. [Full Text] [PDF]

				T. Milovanova, S. Chatterjee, Y. Manevich, I. Kotelnikova, K. DeBolt, M. Madesh, J. S. Moore, and A. B. Fisher Lung endothelial cell proliferation with decreased shear stress is mediated by reactive oxygen species Am J Physiol Cell Physiol, January 1, 2006; 290(1): C66 - C76. [Abstract] [Full Text] [PDF]

				M. F. McCarty and K. I. Block Multifocal Angiostatic Therapy: An Update Integr Cancer Ther, December 1, 2005; 4(4): 301 - 314. [Abstract] [PDF]