Journal article
Subfornical Organ Mediates Sympathetic and Hemodynamic Responses to Blood-Borne Proinflammatory Cytokines
Hypertension (Dallas, Tex. 1979), Vol.62(1), pp.118-125
07/2013
DOI: 10.1161/HYPERTENSIONAHA.113.01404
PMID: 23670302
Abstract
Proinflammatory cytokines play an important role in regulating autonomic and cardiovascular function in hypertension and heart failure. Peripherally administered proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), act on the brain to increase blood pressure, heart rate, and sympathetic nerve activity. These molecules are too large to penetrate the blood-brain barrier, and so the mechanisms by which they elicit these responses remain unknown. We tested the hypothesis that the subfornical organ (SFO), a forebrain circumventricular organ that lacks a blood-brain barrier, plays a major role in mediating the sympathetic and hemodynamic responses to circulating proinflammatory cytokines. Intracarotid artery injection of TNF-α (200 ng) or IL-1β (200 ng) dramatically increased mean blood pressure, heart rate, and renal sympathetic nerve activity in rats with sham lesions of the SFO (SFO-s). These excitatory responses to intracarotid artery TNF-α and IL-1β were significantly attenuated in SFO-lesioned (SFO-x) rats. Similarly, the increases in mean blood pressure, heart rate, and renal sympathetic nerve activity in response to intravenous injections of TNF-α (500 ng) or IL-1β (500 ng) in SFO-s rats were significantly reduced in the SFO-x rats. Immunofluorescent staining revealed a dense distribution of the p55 TNF-α receptor and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, in the SFO. These data suggest that SFO is a predominant site in the brain at which circulating proinflammatory cytokines act to elicit cardiovascular and sympathetic responses.
Details
- Title: Subtitle
- Subfornical Organ Mediates Sympathetic and Hemodynamic Responses to Blood-Borne Proinflammatory Cytokines
- Creators
- Shun-Guang Wei - From the Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA (S.-G.W., Z.-H.Z., Y.Y., R.B.F.); Department of Psychology, University of Iowa, Iowa City, IA (T.G.B., A.K.J.); and Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)Zhi-Hua Zhang - From the Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA (S.-G.W., Z.-H.Z., Y.Y., R.B.F.); Department of Psychology, University of Iowa, Iowa City, IA (T.G.B., A.K.J.); and Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)Terry G Beltz - From the Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA (S.-G.W., Z.-H.Z., Y.Y., R.B.F.); Department of Psychology, University of Iowa, Iowa City, IA (T.G.B., A.K.J.); and Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)Yang Yu - From the Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA (S.-G.W., Z.-H.Z., Y.Y., R.B.F.); Department of Psychology, University of Iowa, Iowa City, IA (T.G.B., A.K.J.); and Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)Alan Kim Johnson - From the Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA (S.-G.W., Z.-H.Z., Y.Y., R.B.F.); Department of Psychology, University of Iowa, Iowa City, IA (T.G.B., A.K.J.); and Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)Robert B Felder - From the Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA (S.-G.W., Z.-H.Z., Y.Y., R.B.F.); Department of Psychology, University of Iowa, Iowa City, IA (T.G.B., A.K.J.); and Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.62(1), pp.118-125
- DOI
- 10.1161/HYPERTENSIONAHA.113.01404
- PMID
- 23670302
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 07/2013
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984002371602771
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