Journal article
Mineralocorticoid receptors, inflammation and sympathetic drive in a rat model of systolic heart failure
Experimental physiology, Vol.95(1), pp.19-25
01/2010
DOI: 10.1113/expphysiol.2008.045948
PMCID: PMC2917189
PMID: 19648480
Abstract
Appreciation for the role of aldosterone and mineralocorticoid receptors in cardiovascular disease is accelerating rapidly. Recent experimental work has unveiled a strong relationship between brain mineralocorticoid receptors and sympathetic drive, an important determinant of outcome in heart failure and hypertension. Two putative mechanisms are explored in this manuscript. First, brain mineralocorticoid receptors may influence sympathetic discharge by regulating the release of pro-inflammatory cytokines into the circulation. Blood-borne pro-inflammatory cytokines act upon receptors in the microvasculature of the brain to induce cyclooxygenase-2 activity and the production of prostaglandin E(2), which penetrates the blood-brain barrier to activate the sympathetic nervous system. Second, brain mineralocorticoid receptors may influence sympathetic drive by upregulating the activity of the brain renin-angiotensin system, resulting in NAD(P)H oxidase-dependent superoxide production. A potential role for superoxide-dependent mitogen-activated protein kinase signalling pathways in the regulation of sympathetic nerve activity is also considered. Other potential downstream signalling mechanisms contributing to mineralocorticoid receptor-mediated sympathetic excitation are under investigation.
Details
- Title: Subtitle
- Mineralocorticoid receptors, inflammation and sympathetic drive in a rat model of systolic heart failure
- Creators
- Robert B Felder - Division of Cardiovascular Medicine, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. robert-felder@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Experimental physiology, Vol.95(1), pp.19-25
- Publisher
- England
- DOI
- 10.1113/expphysiol.2008.045948
- PMID
- 19648480
- PMCID
- PMC2917189
- ISSN
- 0958-0670
- eISSN
- 1469-445X
- Grant note
- R01HL73986 / NHLBI NIH HHS R01 HL063915 / NHLBI NIH HHS R01HL063915 / NHLBI NIH HHS R01 HL073986 / NHLBI NIH HHS R01 HL073986-04 / NHLBI NIH HHS R01 HL073986-05A2 / NHLBI NIH HHS R01 HL063915-05 / NHLBI NIH HHS R01 HL073986-03 / NHLBI NIH HHS
- Language
- English
- Date published
- 01/2010
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984065495402771
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