AT1 Receptors in the Collecting Duct Directly Modulate the Concentration of Urine
- 1 December 2011
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 22 (12), 2237-2246
- https://doi.org/10.1681/asn.2010101095
Abstract
Mice lacking AT1 angiotensin receptors have an impaired capacity to concentrate the urine, but the underlying mechanism is unknown. To determine whether direct actions of AT1 receptors in epithelial cells of the collecting duct regulate water reabsorption, we used Cre-Loxp technology to specifically eliminate AT1A receptors from the collecting duct in mice (CD-KOs). Although levels of AT1A receptor mRNA in the inner medulla of CD-KO mice were significantly reduced, their kidneys appeared structurally normal. Under basal conditions, plasma and urine osmolalities and urine volumes were similar between CD-KO mice and controls. The increase in urine osmolality in response to water deprivation or vasopressin administration, however, was consistently attenuated in CD-KO mice. Similarly, levels of aquaporin-2 protein in inner and outer medulla after water deprivation were significantly lower in CD-KO mice compared with controls, despite its normal localization to the apical membrane. In summary, these results demonstrate that AT1A receptors in epithelial cells of the collecting duct directly modulate aquaporin-2 levels and contribute to the concentration of urine.Keywords
This publication has 39 references indexed in Scilit:
- Molecular mechanisms of angiotensin II stimulation on aquaporin-2 expression and traffickingAmerican Journal of Physiology-Renal Physiology, 2011
- AT1A Angiotensin Receptors in the Renal Proximal Tubule Regulate Blood PressureCell Metabolism, 2011
- Angiotensin II Type 1A Receptors in Vascular Smooth Muscle Cells Do Not Influence Aortic Remodeling in HypertensionHypertension, 2011
- αENaC-Mediated Lithium Absorption Promotes Nephrogenic Diabetes InsipidusJournal of the American Society of Nephrology, 2011
- Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentrationAmerican Journal of Physiology-Renal Physiology, 2010
- Changes of renal AQP2, ENaC, and NHE3 in experimentally induced heart failure: response to angiotensin II AT1receptor blockadeAmerican Journal of Physiology-Renal Physiology, 2009
- AT1a receptor knockout in mice impairs urine concentration by reducing basal vasopressin levels and its receptor signaling proteins in the inner medullaKidney International, 2009
- Enhanced Distal Nephron Sodium Reabsorption in Chronic Angiotensin II–Infused MiceHypertension, 2009
- Local production of angiotensin II in the subfornical organ causes elevated drinkingJCI Insight, 2007
- Altered blood pressure responses and normal cardiac phenotype in ACE2-null miceJCI Insight, 2006