Journal article
Increased cyclooxygenase-2 expression in hypothalamic paraventricular nucleus in rats with heart failure : Role of nuclear factor κB
Hypertension (Dallas, Tex. 1979), Vol.49(3), pp.511-518
2007
DOI: 10.1161/01.HYP.0000257356.20527.c5
PMID: 17242297
Abstract
We investigated the role of nuclear factor κB (NF-κB) in the cytokine-mediated induction of cyclooxygenase-2 activity in the paraventricular nucleus of hypothalamus (PVN), a critical cardiovascular and autonomic center, in rats with heart failure (HF). Sprague–Dawley rats underwent coronary artery ligation to induce HF or sham surgery. HF rats were treated orally for 6 weeks with vehicle (tap water), the NF-κB inhibitor pyrrolidine dithiocarbamate (150 mg/kg per day), or the mineralocorticoid receptor antagonist eplerenone (30 mg/kg per day), which has been shown to reduce circulating proinflammatory cytokines in this model. Compared with sham surgery, HF rats had higher (P<0.05) levels of aldosterone, interleukin-1β and norepinephrine in plasma and prostaglandin E2 in cerebrospinal fluid. In the PVN, NF-κB p50 precursor p105 mRNA increased, and mRNA for its inhibitor, IκB, decreased (P<0.05). Cyclooxygenase-2 mRNA and protein expression was increased in perivascular cells of the PVN. Both pyrrolidine dithiocarbamate and eplerenone reduced (P<0.05) p105 mRNA and increased IκB mRNA in PVN. Both also reduced (P<0.05) cyclooxygenase-2 mRNA and protein expression in PVN, cerebrospinal fluid prostaglandin E2, and plasma norepinephrine. Eplerenone, but not pyrrolidine dithiocarbamate, reduced plasma interleukin-1β. Pyrrolidine dithiocarbamate and eplerenone had no effect on plasma aldosterone. The results suggest that activation of NF-κB is an intermediary step in cytokine-mediated induction of cyclooxygenase-2 in the PVN of HF rats. By enhancing access of prostaglandin E2 to hypothalamic neurons, this mechanism may contribute to augmented sympathetic nerve activity in HF.
Details
- Title: Subtitle
- Increased cyclooxygenase-2 expression in hypothalamic paraventricular nucleus in rats with heart failure : Role of nuclear factor κB
- Creators
- Yang Yu - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesYu-Ming KANG - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesZhi-Hua ZHANG - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesShun-Guang WEI - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesYi Chu - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesRobert M WEISS - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesRobert B FELDER - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.49(3), pp.511-518
- Publisher
- Lippincott; Philadelphia, PA; Hagerstown, MD
- DOI
- 10.1161/01.HYP.0000257356.20527.c5
- PMID
- 17242297
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 2007
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984065389802771
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