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: 295/1/H227    most recent 01157.2007v1 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 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 Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Kang, Y.-M. Articles by Felder, R. B. Search for Related Content PubMed PubMed Citation Articles by Kang, Y.-M. Articles by Felder, R. B.

Inhibition of brain proinflammatory cytokine synthesis reduces hypothalamic excitation in rats with ischemia-induced heart failure

¹Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine and ²Department of Psychology, University of Iowa and ³Department of Veterans Affairs Medical Center, Iowa City, Iowa

Submitted 5 October 2007 ; accepted in final form 14 May 2008

The expression of proinflammatory cytokines increases in the hypothalamus of rats with heart failure (HF). The pathophysiological significance of this observation is unknown. We hypothesized that hypothalamic proinflammatory cytokines upregulate the activity of central neural systems that contribute to increased sympathetic nerve activity in HF, specifically, the brain renin-angiotensin system (RAS) and the hypothalamic-pituitary-adrenal (HPA) axis. Rats with HF induced by coronary ligation and sham-operated controls (SHAM) were treated for 4 wk with a continuous intracerebroventricular infusion of the cytokine synthesis inhibitor pentoxifylline (PTX, 10 µg/h) or artificial cerebrospinal fluid (VEH). In VEH-treated HF rats, compared with VEH-treated SHAM rats, the hypothalamic expression of proinflammatory cytokines was increased, along with key components of the brain RAS (renin, angiotensin-converting enzyme, angiotensin type 1 receptor) and corticotropin-releasing hormone, the central indicator of HPA axis activation, in the paraventricular nucleus (PVN) of the hypothalamus. The expression of other inflammatory/excitatory mediators (superoxide, prostaglandin E₂) was also increased, along with evidence of chronic neuronal excitation in PVN. VEH-treated HF rats had higher plasma levels of norepinephrine, ANG II, interleukin (IL)-1β, and adrenocorticotropic hormone, increased left ventricular end-diastolic pressure, and increased wet lung-to-body weight ratio. With the exception of plasma IL-1β, an indicator of peripheral proinflammatory cytokine activity, all measures of neurohumoral excitation were significantly lower in HF rats treated with intracerebroventricular PTX. These findings suggest that the increase in brain proinflammatory cytokines observed in rats with ischemia-induced HF is functionally significant, contributing to neurohumoral excitation by activating brain RAS and the HPA axis.

paraventricular nucleus of hypothalamus; inflammation; sympathetic nervous system; brain renin-angiotensin system; hypothalamic-pituitary-adrenal axis

This article has been cited by other articles:

				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]

				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]