# Neural Regulation of Vasopressin Release in a Model of Dilutional Hyponatremia

> **NIH NIH R01** · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2020 · $560,112

## Abstract

Purpose: Hyponatremia is the most common electrolyte disorder and in 2006 the cost of treating
hyponatremia in the US was estimated to be $1.6-$3.6 billion per year. Inappropriate vasopressin
secretion is the major cause of dilutional hyponatremia associated with liver and heart failure.
Brain derived neurotrophic factor (BDNF) and its receptor TrkB are expressed by magnocellular
neurosectory cells that secrete vasopressin into circulation. Our studies will be among the first to
test the role of the BDNF-TrkB signaling in an animal model of inappropriate vasopressin release.
We propose that in an animal model of liver failure activity pendent stimulation of the BDNF-TrkB
system increases vasopressin release by changing chloride transport preventing or reversing Cl-
inhibition.
Our hypotheses will be tested with the following Specific Aims:
 1. To determine if norepinephrine inputs support chronic activation of AVP neurons in the
 SON of male bile duct ligated rats.
 2. To determine if BDNF links the increased activation of AVP neurons to the changes in
 chloride transport loss of inhibition.
 3. To test the role of estrogen in preventing AVP release in female BDL rats.
Methods: The studies will employ Western blot and co-immunoprecipitation in combination with
immunohistochemistry and laser capture microdissection RT-PCR, metabolism cage studies to
measure urine and sodium excretion, DREADD, shRNA site-specific knockdown, and in vitro
electrophysiology to test these hypotheses.
Benefit: These experiments will address an existing gap in our understanding of
neurophypophyseal function and the pathogenesis of hyponatremia. The findings of these
experiments could potentially alter the way that inappropriate vasopressin release is studied and
conceptualized clinically.

## Key facts

- **NIH application ID:** 9895545
- **Project number:** 5R01HL142341-03
- **Recipient organization:** UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
- **Principal Investigator:** J Thomas Cunningham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $560,112
- **Award type:** 5
- **Project period:** 2018-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895545

## Citation

> US National Institutes of Health, RePORTER application 9895545, Neural Regulation of Vasopressin Release in a Model of Dilutional Hyponatremia (5R01HL142341-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9895545. Licensed CC0.

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