Abstract
Brain pro‐inflammatory cytokines contribute to sympathetic drive in heart failure
The FASEB journal, Vol.21(6), pp.A1266-A1266
2007
DOI: 10.1096/fasebj.21.6.A1266-c
Abstract
The pro‐inflammatory cytokines (PIC) are increased in plasma, heart and brain in rats with ischemia‐induced heart failure (HF). An open question is whether brain PIC contribute to augmented sympathetic drive in HF. Rats underwent coronary ligation (CL) to induce HF, with left ventricular (LV) ejection fraction by echocardiography 35.9±4.1% (normal:≈80%). They received either the cytokine synthesis inhibitor pentoxifylline (PTX, 10 μg/hr, ICV) beginning the day after CL or no treatment. At week 4, they underwent anesthesia for hemodynamic measurement and collection of plasma and tissue samples. LV end‐diastolic pressure was lower (∗P<0.05) in PTX treated than untreated rats (9.6±1.5∗ vs 20.6±1.7 mmHg), but heart rate, arterial pressure and pulse pressure were unaffected. PTX‐treated rats had lower lung/body weight (BW) ratio than untreated rats, but right ventricle/BW ratio and LV function were unaffected. TNF‐α in hypothalamus (4.3±0.4∗ vs 7.1±0.5 pg/mg protein) and brainstem (3.4±0.4∗ vs 6.6±0.5 pg/mg protein), and IL‐1β in hypothalamus (33.2±3.9∗ vs 50.2±4.6 pg/mg protein) were lower (by ELISA) in PTX‐treated than untreated rats. Immunohistochemistry revealed less microglial activation and reduced angiotensin type‐1 receptors, angiotensin converting enzyme, cyclooxygenase‐2 and superoxide in paraventricular nucleus of hypothalamus in PTX‐treated than untreated rats. Plasma norepinephine was lower (234.2±9.3∗ vs 266.8±11.7 pg/ml) in PTX‐treated than untreated rats, but plasma PIC levels were unaffected. The results suggest that brain PIC stimulate neuro‐excitatory systems, including the brain renin‐angiotensin system, that contribute to sympathetic drive in heart failure.
Support: NIH HL‐073986.
Details
- Title: Subtitle
- Brain pro‐inflammatory cytokines contribute to sympathetic drive in heart failure
- Creators
- Yu‐Ming KangZhi‐Hua ZhangBaojian Xue - University of IowaRobert M Weiss - Veterans Affairs Medical CenterAlan Kim Johnson - University of IowaRobert B Felder - Veterans Affairs Medical Center
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.21(6), pp.A1266-A1266
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.21.6.A1266-c
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 2007
- Academic Unit
- Neuroscience and Pharmacology; Health and Human Physiology; Internal Medicine; Iowa Neuroscience Institute; Cardiovascular Medicine; Psychological and Brain Sciences; Neurology (Pediatrics)
- Record Identifier
- 9984071633502771
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