Abstract
Tumor Necrosis Factor‐α Receptor 1 (TNFR1) Knockdown in Subfornical Organ (SFO) Reduces Sympathetic and Hemodynamic Responses to Blood‐Borne TNF‐α
The FASEB journal, Vol.29(S1), p.987.6
04/2015
DOI: 10.1096/fasebj.29.1_supplement.987.6
Abstract
We recently reported that the SFO, a forebrain circumventricular organ that lacks a blood-brain barrier, plays a major role in mediating sympathetic and hemodynamic responses to blood-borne proinflammatory cytokines (PICs). Blood-borne PICs upregulate inflammation and renin-angiotensin system (RAS) activity in cardiovascular regions of the brain to activate the sympathetic nervous system, but the underlying mechanisms are not fully understood. We tested the contribution of TNFR1 in the SFO to the sympathetic and hemodynamic responses elicited by blood-borne TNF-α. Rats received SFO microinjections of a TNFR1 shRNA or scrambled shRNA lentiviral vector, or vehicle. Two weeks later, RT-PCR showed that TNFR1 shRNA reduced TNFR1 mRNA by 43% (p<0.05) in the SFO but not in the paraventricular nucleus (PVN). Intracarotid artery injection of TNF-α (200 ng) increased blood pressure, heart rate, and renal sympathetic nerve activity in rats treated with scrambled shRNA or vehicle. These excitatory responses to TNF-α were attenuated (p<0.05) in rats treated with TNFR1 shRNA. Four hours after TNF-α injection, mRNA for NF-κB, cyclooxygenase-2 and angiotensin II type 1 receptor had increased in both SFO and PVN in rats treated with scrambled shRNA or vehicle. In rats treated with SFO TNFR1 shRNA, the TNF-α-induced increases in these parameters were reduced (p<0.05) not only in SFO but also in PVN. These data suggest that blood-borne TNF-α acts upon TNFR1 in SFO to upregulate inflammation and RAS activity in SFO, with downstream effects on excitatory mediators in the PVN that contribute to sympathetic excitation. Supported by NIH Grants HL-073986 and HL-096671 and Department of Veterans Affairs.
Details
- Title: Subtitle
- Tumor Necrosis Factor‐α Receptor 1 (TNFR1) Knockdown in Subfornical Organ (SFO) Reduces Sympathetic and Hemodynamic Responses to Blood‐Borne TNF‐α
- Creators
- Yang Yu - University of IowaShunguang WeiRobert Felder - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.29(S1), p.987.6
- DOI
- 10.1096/fasebj.29.1_supplement.987.6
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: HL‐073986, HL‐096671; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs
- Language
- English
- Date published
- 04/2015
- Academic Unit
- Internal Medicine; Cardiovascular Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984256793502771
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