title: Enhanced water and salt intake in transgenic mice with brain-restricted overexpression of angiotensin (AT1) receptors.
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.
authors.affiliation: Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, Iowa, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Lazartigues
authors.forename: Puspha
authors.initials: P
authors.lastname: Sinnayah
authors.forename: Ginette
authors.initials: G
authors.lastname: Augoyard
authors.forename: Claude
authors.initials: C
authors.lastname: Gharib
authors.forename: Alan Kim
authors.initials: AK
authors.lastname: Johnson
authors.forename: Robin L
authors.initials: RL
authors.lastname: Davisson