Abstract
Brain COX2 and Prostaglandin EP3 Receptors Mediate the Sympathetic Response to Blood‐borne TNF‐α in Rats
The FASEB journal, Vol.25, pp.845.1-845.1
04/2011
DOI: 10.1096/fasebj.25.1_supplement.845.1
Abstract
Blood‐borne pro‐inflammatory cytokines act upon the central nervous system to increase sympathetic drive in normal rats and rats with ischemia‐induced heart failure. Possible mechanisms have been suggested but the underlying pathways are still poorly understood. We tested the hypothesis that central cyclooxygenase‐2 (COX2), a potential source of prostaglandin E2 (PGE2), and the PGE2 EP3 receptor, mediate the sympatho‐excitatory responses induced by TNF‐α. In urethane‐anesthetized rats, a centrally directed intracarotid artery (ICA) injection of TNF‐α elicited significant (p<0.05) increases in hypothalamic paraventricular nucleus (PVN) COX2 mRNA and CSF PGE2 level and in renal sympathetic nerve activity (RSNA), mean blood pressure (MBP) and heart rate (HR). Intracerebroventricular (ICV) pretreatment (10 min) with the COX2 inhibitor NS398 or the EP3 antagonist L798106 prevented the increases in RSNA, MBP and HR induced by ICA TNF‐α; pretreatment with EP1 or EP4 antagonists slightly reduced these responses. Both ICV and PVN injections of PGE2 and EP agonists elicited sympatho‐excitatory responses that were prevented by ICV pretreatment with L798106. These data suggest that blood‐borne TNF‐α induces central COX2‐dependent PGE2 production, and that the sympatho‐excitatory responses to PGE2 are mediated primarily by EP3 receptors. Supported by a VA Merit Review Award and NIH RO1 HL073986.
Details
- Title: Subtitle
- Brain COX2 and Prostaglandin EP3 Receptors Mediate the Sympathetic Response to Blood‐borne TNF‐α in Rats
- Creators
- Zhihua Zhang - University of IowaYang Yu - University of IowaShunguang Wei - University of IowaRobert B Felder - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.25, pp.845.1-845.1
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.25.1_supplement.845.1
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- NIH (RO1 HL073986) VA Merit Review
- Language
- English
- Date published
- 04/2011
- Academic Unit
- Internal Medicine; Iowa Neuroscience Institute; Cardiovascular Medicine
- Record Identifier
- 9984071650002771
Metrics
12 Record Views