Does Aldosterone Upregulate the Brain Renin-Angiotensin System in Rats with Heart Failure?

Yang Yu; Shun-Guang Wei; Zhi-Hua Zhang; Elise Gomez-Sanchez; Robert M Weiss; Robert B Felder

doi:10.1161/HYPERTENSIONAHA.107.099796

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Does Aldosterone Upregulate the Brain Renin-Angiotensin System in Rats with Heart Failure?

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Does Aldosterone Upregulate the Brain Renin-Angiotensin System in Rats with Heart Failure?

Yang Yu, Shun-Guang Wei, Zhi-Hua Zhang, Elise Gomez-Sanchez, Robert M Weiss and Robert B Felder

Hypertension (Dallas, Tex. 1979), Vol.51(3), pp.727-733

03/2008

DOI: 10.1161/HYPERTENSIONAHA.107.099796

PMCID: PMC2790402

PMID: 18227408

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Abstract

The brain renin-angiotensin system (RAS) contributes to increased sympathetic drive in heart failure (HF). The factors upregulating the brain RAS in HF remain unknown. We hypothesized that aldosterone (ALDO), a downstream product of the systemic RAS that crosses the blood-brain barrier, signals the brain to increase RAS activity in HF. We examined the relationship between circulating and brain ALDO in normal intact rats, in adrenalectomized rats receiving subcutaneous infusions of ALDO, and in rats with ischemia-induced HF and sham-operated controls (SHAM). Brain ALDO levels were proportional to plasma ALDO levels across the spectrum of rats studied. Compared with SHAM rats, HF rats had higher plasma and hypothalamic tissue levels of ALDO. HF rats also had higher expression of mRNA and protein for angiotensin converting enzyme (ACE) and angiotensin type 1 receptors (AT1-R) in hypothalamus, increased reduced nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase activity and superoxide generation in paraventricular nucleus (PVN) of hypothalamus, increased excitation of PVN neurons, and increased plasma norepinephrine (NE). HF rats treated for 4 weeks with intracerebroventricular RU28318 (1 μg/hr), a selective mineralocorticoid receptor antagonist, had less hypothalamic ACE and AT1-R mRNA and protein, less NAD(P)H-induced superoxide in PVN, fewer excited PVN neurons, and lower plasma NE. RU28318 had no effect on plasma ALDO, or on ACE or AT1-R mRNA expression in brain cortex. The data demonstrate that ALDO of adrenal origin enters the hypothalamus in direct proportion to plasma levels, and suggest that ALDO contributes to the upregulation of hypothalamic RAS activity and sympathetic drive in heart failure.

angiotensin type 1 receptor

sympathetic nerve activity

angiotensin converting enzyme

superoxide

hypothalamus

Details

Title: Subtitle: Does Aldosterone Upregulate the Brain Renin-Angiotensin System in Rats with Heart Failure?
Creators: Yang Yu - Department of Internal Medicine, University of Iowa Iowa City, IA, 52242
Shun-Guang Wei - Department of Internal Medicine, University of Iowa Iowa City, IA, 52242
Zhi-Hua Zhang - Department of Internal Medicine, University of Iowa Iowa City, IA, 52242
Elise Gomez-Sanchez - Department of Medicine, University of Mississippi and Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center Jackson, MS, 39216
Robert M Weiss - Department of Internal Medicine, University of Iowa Iowa City, IA, 52242
Robert B Felder - Department of Internal Medicine, University of Iowa Iowa City, IA, 52242
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.51(3), pp.727-733
DOI: 10.1161/HYPERTENSIONAHA.107.099796
PMID: 18227408
PMCID: PMC2790402
NLM abbreviation: Hypertension
ISSN: 0194-911X
eISSN: 1524-4563
Language: English
Date published: 03/2008
Academic Unit: Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984065492202771

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