Journal article
Sodium appetite and thirst do not require angiotensinogen production in astrocytes or hepatocytes
The Journal of physiology, Vol.601(16), pp.3499-3532
08/15/2023
DOI: 10.1113/JP283169
Appears in UI Libraries Support Open Access
Abstract
In addition to its renal and cardiovascular functions, angiotensin signaling is thought to be responsible for the increases in salt and water intake caused by hypovolemia. However, it remains unclear whether these behaviors require angiotensin production in the brain or liver. Here, we use in situ hybridization to identify tissue-specific expression of the genes required for producing angiotensin peptides, then use conditional genetic deletion of angiotensinogen (Agt) to test whether production in the brain or liver is necessary for sodium appetite and thirst. In the mouse brain, we identified expression of Agt (the precursor of all angiotensin peptides) in a large subset of astrocytes. We also identified Ren1 and Ace (enzymes required to produce angiotensin II) in the choroid plexus, and Ren1 in neurons within the nucleus ambiguus compact formation. In the liver, we confirmed that Agt is expressed in widespread hepatocytes. We next tested whether thirst and sodium appetite require angiotensinogen production in astrocytes or hepatocytes. Despite virtually eliminating expression in the brain, deleting astrocytic Agt did not reduce thirst or sodium appetite. Despite markedly reducing angiotensinogen in the blood, eliminating Agt from hepatocytes did not reduce thirst or sodium appetite, and in fact, these mice consumed the largest amounts of salt and water after sodium deprivation. Deleting Agt from both astrocytes and hepatocytes also did not prevent thirst or sodium appetite. Our findings suggest that angiotensin signaling is not required for sodium appetite or thirst and highlight the need to identify alternative signaling mechanisms.
Details
- Title: Subtitle
- Sodium appetite and thirst do not require angiotensinogen production in astrocytes or hepatocytes
- Creators
- Lila Peltekian - University of IowaSilvia Gasparini - University of IowaFrederico S Fazan - University of IowaSamyukta Karthik - University of IowaGabrielle Iverson - University of IowaJon M Resch - University of IowaJoel C Geerling - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.601(16), pp.3499-3532
- DOI
- 10.1113/JP283169
- eISSN
- 1469-7793
- Publisher
- Wiley
- Grant note
- DOI: 10.13039/100008893, name: University of Iowa
- Language
- English
- Electronic publication date
- 06/08/2023
- Date published
- 08/15/2023
- Academic Unit
- Neurology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984430177102771
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