Enhanced water and salt intake in transgenic mice with brain-restricted overexpression of angiotensin (AT1) receptors

Eric Lazartigues; Puspha Sinnayah; Ginette Augoyard; Claude Gharib; Alan Kim Johnson; Robin L Davisson

doi:10.1152/ajpregu.00751.2007

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Enhanced water and salt intake in transgenic mice with brain-restricted overexpression of angiotensin (AT1) receptors

Journal article

Open access

Peer reviewed

Enhanced water and salt intake in transgenic mice with brain-restricted overexpression of angiotensin (AT1) receptors

Eric Lazartigues, Puspha Sinnayah, Ginette Augoyard, Claude Gharib, Alan Kim Johnson and Robin L Davisson

American journal of physiology. Regulatory, integrative and comparative physiology, Vol.295(5), pp.R1539-1545

11/2008

DOI: 10.1152/ajpregu.00751.2007

PMCID: PMC2584862

PMID: 18753266

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Abstract

To address the relative contribution of central and peripheral angiotensin II (ANG II) type 1A receptors (AT(1A)) to blood pressure and volume homeostasis, we generated a transgenic mouse model [neuron-specific enolase (NSE)-AT(1A)] with brain-restricted overexpression of AT(1A) receptors. These mice are normotensive at baseline but have dramatically enhanced pressor and bradycardic responses to intracerebroventricular ANG II or activation of endogenous ANG II production. Here our goal was to examine the water and sodium intake in this model under basal conditions and in response to increased ANG II levels. Baseline water and NaCl (0.3 M) intakes were significantly elevated in NSE-AT(1A) compared with nontransgenic littermates, and bolus intracerebroventricular injections of ANG II (200 ng in 200 nl) caused further enhanced water intake in NSE-AT(1A). Activation of endogenous ANG II production by sodium depletion (10 days low-sodium diet followed by furosemide, 1 mg sc) enhanced NaCl intake in NSE-AT(1A) mice compared with wild types. Fos immunohistochemistry, used to assess neuronal activation, demonstrated sodium depletion-enhanced activity in the anteroventral third ventricle region of the brain in NSE-AT(1A) mice compared with control animals. The results show that brain-selective overexpression of AT(1A) receptors results in enhanced salt appetite and altered water intake. This model provides a new tool for studying the mechanisms of brain AT(1A)-dependent water and salt consumption.

Angiotensin II - blood

Angiotensin II - pharmacology

Animals

Appetite - genetics

DNA, Complementary - biosynthesis

DNA, Complementary - genetics

Drinking - genetics

Electrolytes - metabolism

Female

Immunohistochemistry

Injections, Intraventricular

Male

Mice

Mice, Transgenic

Neurons - physiology

Phosphopyruvate Hydratase - genetics

Proto-Oncogene Proteins c-fos - metabolism

Receptor, Angiotensin, Type 1 - genetics

Receptor, Angiotensin, Type 1 - physiology

Sodium - deficiency

Sodium, Dietary - pharmacology

Thirst - physiology

Vasoconstrictor Agents - blood

Vasoconstrictor Agents - pharmacology

Vasopressins - metabolism

Details

Title: Subtitle: Enhanced water and salt intake in transgenic mice with brain-restricted overexpression of angiotensin (AT1) receptors
Creators: Eric Lazartigues - Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, Iowa, USA
Puspha Sinnayah
Ginette Augoyard
Claude Gharib
Alan Kim Johnson
Robin L Davisson
Resource Type: Journal article
Publication Details: American journal of physiology. Regulatory, integrative and comparative physiology, Vol.295(5), pp.R1539-1545
DOI: 10.1152/ajpregu.00751.2007
PMID: 18753266
PMCID: PMC2584862
NLM abbreviation: Am J Physiol Regul Integr Comp Physiol
ISSN: 0363-6119
eISSN: 1522-1490
Grant note: HL 84624 / NHLBI NIH HHS HL 14388 / NHLBI NIH HHS HL 63887 / NHLBI NIH HHS
Language: English
Date published: 11/2008
Academic Unit: Psychological and Brain Sciences; Neuroscience and Pharmacology; Health, Sport, and Human Physiology
Record Identifier: 9984213411502771

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