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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 678484, 9 pages
http://dx.doi.org/10.1155/2013/678484
Research Article

Nitroglycerine-Induced Nitrate Tolerance Compromises Propofol Protection of the Endothelial Cells against TNF-α: The Role of PKC-β2 and NADPH Oxidase

1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
2Department of Anesthesiology, University of Hong Kong, Hong Kong
3Department of Cardiac Surgery, Chongqing Zhongshan Hospital, Chongqing 400013, China
4Department of Anesthesia, Chongqing Zhongshan Hospital, Chongqing 400013, China
5Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China

Received 10 September 2013; Accepted 18 October 2013

Academic Editor: Yanfang Chen

Copyright © 2013 Shaoqing Lei et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Continuous treatment with organic nitrates causes nitrate tolerance and endothelial dysfunction, which is involved with protein kinase C (PKC) signal pathway and NADPH oxidase activation. We determined whether chronic administration with nitroglycerine compromises the protective effects of propofol against tumor necrosis factor (TNF-) induced toxicity in endothelial cells by PKC-β2 dependent NADPH oxidase activation. Primary cultured human umbilical vein endothelial cells were either treated or untreated with TNF-α (40 ng/mL) alone or in the presence of the specific PKC-β2 inhibitor CGP53353 (1 μM)), nitroglycerine (10 μM), propofol (100 μM), propofol plus nitroglycerin, or CGP53353 plus nitroglycerine, respectively, for 24 hours. TNF-α increased the levels of superoxide, Nox (nitrate and nitrite), malondialdehyde, and nitrotyrosine production, accompanied by increased protein expression of p-PKC-β2, gP91phox, and endothelial cell apoptosis, whereas all these changes were further enhanced by nitroglycerine. CGP53353 and propofol, respectively, reduced TNF-α induced oxidative stress and cell toxicity. CGP53353 completely prevented TNF-α induced oxidative stress and cell toxicity in the presence or absence of nitroglycerine, while the protective effects of propofol were neutralized by nitroglycerine. It is concluded that nitroglycerine comprises the protective effects of propofol against TNF-α stimulation in endothelial cells, primarily through PKC-β2 dependent NADPH oxidase activation.