AJP - Heart Calcium Transients and Cell-Sarcomere
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 293: H599-H609, 2007. First published April 6, 2007; doi:10.1152/ajpheart.00286.2007
0363-6135/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
293/1/H599    most recent
00286.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guggilam, A.
Right arrow Articles by Francis, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guggilam, A.
Right arrow Articles by Francis, J.

TNF-{alpha} blockade decreases oxidative stress in the paraventricular nucleus and attenuates sympathoexcitation in heart failure rats

Anuradha Guggilam,1 Masudul Haque,1 Edmund Kenneth Kerut,2 Elizabeth McIlwain,2 Pamela Lucchesi,2 Inder Seghal,1 and Joseph Francis1,2

1Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge; and 2Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Submitted 7 March 2007 ; accepted in final form 30 March 2007

Oxidative stress plays an important role in the pathophysiology of cardiovascular disease. Recent evidence suggests that cytokines induce oxidative stress and contribute to cardiac dysfunction. In this study, we investigated whether increased circulating and tissue levels of tumor necrosis factor (TNF)-{alpha} in congestive heart failure (CHF) modulate the expression of NAD(P)H oxidase subunits, Nox2 and its isoforms, in the paraventricular nucleus (PVN) of the hypothalamus and contribute to exaggerated sympathetic drive in CHF. Heart failure was induced in Sprague-Dawly rats by coronary artery ligation and was confirmed using echocardiography. Pentoxifylline (PTX) was used to block the production of cytokines for a period of 5 wk. CHF induced a significant increase in the production of reactive oxygen species (ROS) in the left ventricle (LV) and in the PVN. The mRNA and protein expression of TNF-{alpha}, Nox1, Nox2, and Nox4 was significantly increased in the LV and PVN of CHF rats. CHF also decreased ejection fraction, increased Tei index, and increased circulating catecholamines (epinephrine and norepinephrine) and renal sympathetic activity (RSNA). In contrast, treatment with PTX in CHF rats completely blocked oxidative stress and decreased the production of TNF-{alpha} and Nox2 isoforms both in the LV and PVN. PTX treatment also decreased catecholamines and RSNA and prevented further decrease in cardiac function. In summary, TNF-{alpha} blockade attenuates ROS and sympathoexcitation in CHF. This study unveils new mechanisms by which cytokines play a role in the pathogenesis of CHF, thus underscoring the importance of targeting cytokines in heart failure.

congestive heart failure; nervous system; cytokines; reactive oxygen species; tumor necrosis factor-{alpha}


Address for reprint requests and other correspondence: J. Francis, Louisiana State Univ., School of Veterinary Medicine, Comparative Biomedical Sciences Dept., 1909 Skip Bertman Dr., Baton Rouge, LA 70803 (e-mail: jfrancis{at}lsu.edu)




This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
H. Zheng, Y.-F. Li, W. Wang, and K. P. Patel
Enhanced angiotensin-mediated excitation of renal sympathetic nerve activity within the paraventricular nucleus of anesthetized rats with heart failure
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1364 - R1374.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
Y.-M. Kang, R.-L. He, L.-M. Yang, D.-N. Qin, A. Guggilam, C. Elks, N. Yan, Z. Guo, and J. Francis
Brain tumour necrosis factor-{alpha} modulates neurotransmitters in hypothalamic paraventricular nucleus in heart failure
Cardiovasc Res, September 1, 2009; 83(4): 737 - 746.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
Y.-M. Kang, Y. Ma, J.-P. Zheng, C. Elks, S. Sriramula, Z.-M. Yang, and J. Francis
Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension
Cardiovasc Res, June 1, 2009; 82(3): 503 - 512.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Dhingra, A. K. Sharma, D. K. Singla, and P. K. Singal
p38 and ERK1/2 MAPKs mediate the interplay of TNF-{alpha} and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis
Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3524 - H3531.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
N. Mariappan, R. N. Soorappan, M. Haque, S. Sriramula, and J. Francis
TNF-{alpha}-induced mitochondrial oxidative stress and cardiac dysfunction: restoration by superoxide dismutase mimetic Tempol
Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2726 - H2737.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.