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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/R1539    most recent 00751.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Lazartigues, E. Articles by Davisson, R. L. Search for Related Content PubMed PubMed Citation Articles by Lazartigues, E. Articles by Davisson, R. L.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

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

Departments of ¹Anatomy and Cell Biology and ²Psychology, The University of Iowa, Iowa City, Iowa; and ³Environmental Physiology, University Claude Bernard, Lyon, France

Submitted 16 October 2007 ; accepted in final form 23 August 2008

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.

thirst; sodium appetite; transgenic mice; circumventricular organs; volume homeostasis; anteroventral third ventricle

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