Mineralocorticoid receptors, inflammation and sympathetic drive in a rat model of systolic heart failure.

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.

journal_name

Exp Physiol

journal_title

Experimental physiology

authors

Felder RB

doi

10.1113/expphysiol.2008.045948

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

19-25

issue

1

eissn

0958-0670

issn

1469-445X

pii

expphysiol.2008.045948

journal_volume

95

pub_type

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