Journal article
Centrally administered lipopolysaccharide elicits sympathetic excitation via NAD(P)H oxidase-dependent mitogen-activated protein kinase signaling
Journal of hypertension, Vol.28(4), pp.806-816
2010
DOI: 10.1097/HJH.0b013e3283358b6e
PMCID: PMC2929929
PMID: 20027123
Abstract
Objective
The mechanisms by which inflammation activates sympathetic drive in heart failure and hypertension remain ill-defined. In this study, an intracerebroventricular injection of lipopolysaccharide (LPS) was used to induce the expression of cytokines and other inflammatory mediators in the brain, in the absence of other excitatory mediators, and the downstream signaling pathways leading to sympathetic activation were examined using intracerebroventricular injections of blocking or inhibiting agents.
Methods and results
In anesthetized rats, intracerebroventricular injection of LPS (5 μg) increased (P < 0.05) renal sympathetic nerve activity, blood pressure and heart rate. LPS increased (P < 0.05) hypothalamic mRNA for NAD(P)H oxidase subunits p47phox and gp91phox, NAD(P)H oxidase-dependent superoxide generation, hypothalamic mRNA for tumor necrosis factor-α, cyclooxygenase-2 and cerebrospinal fluid levels of tumor necrosis factor-α and prostaglandin E2. In the paraventricular nucleus of hypothalamus, dihydroethidium staining for superoxide expression and c-Fos activity (indicating neuronal excitation) increased. The superoxide scavenger tempol significantly (P < 0.05) diminished the expression of inflammatory mediators, as well as superoxide expression and neuronal excitation in paraventricular nucleus. SB203580 (p38 mitogen-activated protein kinase inhibitor) also reduced the expression of inflammatory mediators in hypothalamus and cerebrospinal fluid. Tempol, apocynin [NAD(P)H oxidase inhibitor], SB203580 and NS398 (cyclooxygenase-2 inhibitor) all reduced cerebrospinal fluid prostaglandin E2 and the sympathoexcitatory response to LPS. LPS also increased angiotensin II type 1 receptor mRNA, a response blocked by apocynin and tempol but not by SB203580.
Conclusion
These findings suggest that central inflammation in pathophysiological conditions activates the sympathetic nervous system via NAD(P)H oxidase and p38 mitogen-activated protein kinase-dependent synthesis of prostaglandin E2.
Details
- Title: Subtitle
- Centrally administered lipopolysaccharide elicits sympathetic excitation via NAD(P)H oxidase-dependent mitogen-activated protein kinase signaling
- Creators
- Zhi-Hua ZHANG - Medical Service, Department of Veterans Affairs Medical Center, University of Iowa, Iowa City, Iowa, United StatesYang Yu - Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United StatesShun-Guang WEI - Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United StatesRobert B FELDER - Medical Service, Department of Veterans Affairs Medical Center, University of Iowa, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Journal of hypertension, Vol.28(4), pp.806-816
- DOI
- 10.1097/HJH.0b013e3283358b6e
- PMID
- 20027123
- PMCID
- PMC2929929
- NLM abbreviation
- J Hypertens
- ISSN
- 0263-6352
- eISSN
- 1473-5598
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- Language
- English
- Date published
- 2010
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984065388902771
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