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

Lazartigues, E, Sinnayah, Puspha, Augoyard, G, Gharib, C, Johnson, A and Davisson, R (2008) Enhanced water and salt intake in transgenic mice with brain-restricted overexpression of angiotensin (AT1) receptors. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 295 (5). R1539-R1545. ISSN 0363-6119

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To address the relative contribution of central and peripheral angiotensin II (ANG II) type 1A receptors (AT1A) to blood pressure and volume homeostasis, we generated a transgenic mouse model [neuron-specific enolase (NSE)-AT1A] with brain-restricted overexpression of AT1A 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-AT1A compared with nontransgenic littermates, and bolus intracerebroventricular injections of ANG II (200 ng in 200 nl) caused further enhanced water intake in NSE-AT1A. 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-AT1A 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-AT1A mice compared with control animals. The results show that brain-selective overexpression of AT1A receptors results in enhanced salt appetite and altered water intake. This model provides a new tool for studying the mechanisms of brain AT1A-dependent water and salt consumption.

Item Type: Article
Additional Information:

Online ISSN: 1522-1490

Uncontrolled Keywords: ResPubID22026. thirst, sodium appetite, circumventricular organs, volume homeostasis, anteroventral third ventricle
Subjects: Historical > Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
Current > FOR Classification > 0601 Biochemistry and Cell Biology
Current > FOR Classification > 0606 Physiology
Depositing User: VUIR
Date Deposited: 26 Apr 2012 03:46
Last Modified: 26 Apr 2012 03:46
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Citations in Scopus: 21 - View on Scopus

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