Abstract
Activation of Brain Peroxisome Proliferator‐Activated Receptor‐γ Inhibits Lipopolysaccharide‐Induced Central Inflammation and Sympathetic Excitation
The FASEB journal, Vol.26(S1), pp. 891.13-891.13
04/2012
DOI: 10.1096/fasebj.26.1_supplement.891.13
Abstract
Inflammation in the brain cardiovascular regulatory regions has recently emerged as an important factor contributing to augmented sympathetic drive in hypertension and heart failure. Activation of peroxisome proliferator-activated receptor (PPAR)-γ, a nuclear transcription factor, has been shown to inhibit inflammation in brain and peripheral tissues. We hypothesized that activation of brain PPAR-γ would inhibit hypothalamic inflammation and sympathetic excitation in response to a lipopolysaccharide (LPS) challenge. In anesthetized rats, intracerebroventricular (ICV) injection of LPS (5 μg) increased (p<0.05, vs baseline) renal sympathetic nerve activity (RSNA, 44.2 ± 7.2 %), mean blood pressure (MBP, 13.9 ± 2.5 mmHg ) and heart rate (HR, 97.2 ± 21.6 bpm). LPS decreased (p<0.05, vs vehicle) PPAR-γ mRNA (−28.7 %) in hypothalamic paraventricular nucleus (PVN), and increased PVN mRNA for tumor necrosis factor-α (311.7 %), interleukin-1β (374.1 %), and cyclooxygenase-2 (341.1 %), as well as cerebrospinal fluid levels of prostaglandin E2 (171.2 %). ICV pretreatment with the PPAR-γ agonist pioglitazone (10 μg) significantly attenuated all of these LPS-induced responses. These data demonstrate that brain PPAR-γ activation counteracts central inflammatory mechanisms leading to sympathetic excitation and so may be an appropriate target for therapeutic intervention in heart failure and hypertension.
Details
- Title: Subtitle
- Activation of Brain Peroxisome Proliferator‐Activated Receptor‐γ Inhibits Lipopolysaccharide‐Induced Central Inflammation and Sympathetic Excitation
- Creators
- Zhihua ZhangYang Yu - Roy J. and Lucille A. Carver College of MedicineShun-Guang Wei - Roy J. and Lucille A. Carver College of MedicineRobert B. Felder - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.26(S1), pp. 891.13-891.13
- DOI
- 10.1096/fasebj.26.1_supplement.891.13
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Language
- English
- Date published
- 04/2012
- Academic Unit
- Cardiovascular Medicine; Internal Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984256799002771
Metrics
2 Record Views