Angiotensin AT 1A receptors expressed in vasopressin-producing cells of the supraoptic nucleus contribute to osmotic control of vasopressin.

Autor:	Sandgren JA; Department of Pharmacology, University of Iowa , Iowa City, Iowa., Linggonegoro DW; Department of Pharmacology, University of Iowa , Iowa City, Iowa., Zhang SY; Department of Pharmacology, University of Iowa , Iowa City, Iowa., Sapouckey SA; Department of Pharmacology, University of Iowa , Iowa City, Iowa., Claflin KE; Department of Pharmacology, University of Iowa , Iowa City, Iowa., Pearson NA; Department of Pharmacology, University of Iowa , Iowa City, Iowa., Leidinger MR; Department of Pathology, University of Iowa , Iowa City, Iowa., Pierce GL; Department of Health and Human Physiology, University of Iowa , Iowa City, Iowa.; Center for Hypertension Research, University of Iowa , Iowa City, Iowa.; François M. Abboud Cardiovascular Research Center, University of Iowa , Iowa City, Iowa., Santillan MK; Department of Obstetrics and Gynecology, University of Iowa , Iowa City, Iowa.; Center for Hypertension Research, University of Iowa , Iowa City, Iowa., Gibson-Corley KN; Department of Pathology, University of Iowa , Iowa City, Iowa.; Center for Hypertension Research, University of Iowa , Iowa City, Iowa.; Fraternal Order of Eagles' Diabetes Research Center, University of Iowa , Iowa City, Iowa., Sigmund CD; Department of Pharmacology, University of Iowa , Iowa City, Iowa.; Center for Hypertension Research, University of Iowa , Iowa City, Iowa.; François M. Abboud Cardiovascular Research Center, University of Iowa , Iowa City, Iowa., Grobe JL; Department of Pharmacology, University of Iowa , Iowa City, Iowa.; Center for Hypertension Research, University of Iowa , Iowa City, Iowa.; François M. Abboud Cardiovascular Research Center, University of Iowa , Iowa City, Iowa.; Iowa Neuroscience Institute, University of Iowa , Iowa City, Iowa.; Obesity Research and Education Initiative, University of Iowa , Iowa City, Iowa.; Fraternal Order of Eagles' Diabetes Research Center, University of Iowa , Iowa City, Iowa.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2018 Jun 01; Vol. 314 (6), pp. R770-R780. Date of Electronic Publication: 2018 Jan 24.
DOI:	10.1152/ajpregu.00435.2017
Abstrakt:	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.
Databáze:	MEDLINE
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