Journal article
Angiotensin AT1A receptors expressed in vasopressin-producing cells of the supraoptic nucleus contribute to osmotic control of vasopressin
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, Vol.314(6), pp.R770-R780
Fluid and Electrolyte Homeostasis
06/01/2018
DOI: 10.1152/ajpregu.00435.2017
PMCID: PMC6032302
PMID: 29364700
Abstract
Angiotensin II (ANG) stimulates the release of arginine vasopressin (AVP) from the neurohypophysis through activation of the AT 1 receptor within the brain, although it remains unclear whether AT 1 receptors expressed on AVP-expressing neurons directly mediate this control. We explored the hypothesis that ANG acts through AT 1A receptors expressed directly on AVP-producing cells to regulate AVP secretion. In situ hybridization and transgenic mice demonstrated localization of AVP and AT 1A mRNA in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN), but coexpression of both AVP and AT 1A mRNA was only observed in the SON. Mice harboring a conditional allele for the gene encoding the AT 1A receptor (AT 1A flox ) were then crossed with AVP-Cre mice to generate mice that lack AT 1A in all cells that express the AVP gene (AT 1A AVP-KO ). AT 1A AVP-KO mice exhibited spontaneously increased plasma and serum osmolality but no changes in fluid or salt-intake behaviors, hematocrit, or total body water. AT 1A AVP-KO mice exhibited reduced AVP secretion (estimated by measurement of copeptin) in response to osmotic stimuli such as acute hypertonic saline loading and in response to chronic intracerebroventricular ANG infusion. However, the effects of these receptors on AVP release were masked by complex stimuli such as overnight dehydration and DOCA-salt treatment, which simultaneously induce osmotic, volemic, and pressor stresses. Collectively, these data support the expression of AT 1A in AVP-producing cells of the SON but not the PVN, and a role for AT 1A receptors in these cells in the osmotic regulation of AVP secretion.
Details
- Title: Subtitle
- Angiotensin AT1A receptors expressed in vasopressin-producing cells of the supraoptic nucleus contribute to osmotic control of vasopressin
- Creators
- Jeremy A Sandgren - University of IowaDanny W Linggonegoro - University of IowaShao Yang Zhang - University of IowaSarah A Sapouckey - University of IowaKristin E Claflin - University of IowaNicole A Pearson - University of IowaMariah R Leidinger - University of IowaGary L Pierce - University of IowaMark K Santillan - University of IowaKatherine N Gibson-Corley - University of IowaCurt D Sigmund - University of IowaJustin L Grobe - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, Vol.314(6), pp.R770-R780
- Series
- Fluid and Electrolyte Homeostasis
- DOI
- 10.1152/ajpregu.00435.2017
- PMID
- 29364700
- PMCID
- PMC6032302
- NLM abbreviation
- Am J Physiol Regul Integr Comp Physiol
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Publisher
- American Physiological Society; Bethesda, MD
- Grant note
- 15SFRN23480000; 15SFRN23730000; 15SFRN23860007; 16PRE30980043; 15UFEL25850040; 18EIA33890055; 15SFRN23760002; 14PRE20380401 / ; ; GM067795 / ; ; UGREF; UGSRF / ; ; HL134850; HL084207 / ; ;
- Alternative title
- AT1A IN AVP NEURONS
- Language
- English
- Date published
- 06/01/2018
- Academic Unit
- Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Pathology; Obstetrics and Gynecology; UI Research Foundation; Neuroscience and Pharmacology; Health, Sport, and Human Physiology ; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9983931212802771
Metrics
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