title: Activation of the renin-angiotensin system, specifically in the subfornical organ is sufficient to induce fluid intake.
abstract: Increased activity of the renin-angiotensin system within the brain elevates fluid intake, blood pressure, and resting metabolic rate. Renin and angiotensinogen are coexpressed within the same cells of the subfornical organ, and the production and action of ANG II through the ANG II type 1 receptor in the subfornical organ (SFO) are necessary for fluid intake due to increased activity of the brain renin-angiotensin system. We generated an inducible model of ANG II production by breeding transgenic mice expressing human renin in neurons controlled by the synapsin promoter with transgenic mice containing a Cre-recombinase-inducible human angiotensinogen construct. Adenoviral delivery of Cre-recombinase causes SFO-selective induction of human angiotensinogen expression. Selective production of ANG II in the SFO results in increased water intake but did not change blood pressure or resting metabolic rate. The increase in water intake was ANG II type 1 receptor-dependent. When given a choice between water and 0.15 M NaCl, these mice increased total fluid and sodium, but not water, because of an increased preference for NaCl. When provided a choice between water and 0.3 M NaCl, the mice exhibited increased fluid, water, and sodium intake, but no change in preference for NaCl. The increase in fluid intake was blocked by an inhibitor of PKC, but not ERK, and was correlated with increased phosphorylated cyclic AMP response element binding protein in the subfornical organ. Thus, increased production and action of ANG II specifically in the subfornical organ are sufficient on their own to mediate an increase in drinking through PKC.
authors: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and.
authors: Jeffrey P
authors: JP
authors: Coble
authors: Department of Anatomy and Cell Biology, Roy J. and Lucille Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors: Martin D
authors: MD
authors: Cassell
authors: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and.
authors: Deborah R
authors: DR
authors: Davis
authors: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and.
authors: Justin L
authors: JL
authors: Grobe
authors: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and curt-sigmund@uiowa.edu.
authors: Curt D
authors: CD
authors: Sigmund
mesh_terms: D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001794:Blood Pressure; D050882:CREB-Binding Protein / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D004327:Drinking Behavior; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D019426:Integrases / Q000235:genetics; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction; D012965:Sodium Chloride / Q000008:administration & dosage; D013356:Subfornical Organ / Q000187:drug effects / Q000201:enzymology*; D016704:Synapsins / Q000235:genetics; D013997:Time Factors
chemical_list: C534931:AGT protein, human; D008164:Luminescent Proteins; D047428:Protein Kinase Inhibitors; D016704:Synapsins; D000808:Angiotensinogen; D012965:Sodium Chloride; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D011493:Protein Kinase C; C045073:Cre recombinase; D019426:Integrases; D012083:Renin
keywords: Cre-recombinase; adenovirus; brain; renin-angiotensin system; subfornical organ