ΔFosB in the supraoptic nucleus contributes to hyponatremia in rats with cirrhosis

Author:

Cunningham J. Thomas1,Nedungadi Thekkethil Prashant1,Walch Joseph D.12,Nestler Eric J.3,Gottlieb Helmut B.4

Affiliation:

1. Department of Integrative Physiology and the Cardiovascular Research Institute, University of North Texas Health Science Centre at Fort Worth, Fort Worth, Texas;

2. Department of Pharmacology and Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas;

3. Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York; and

4. Department of Pharmaceutical Sciences, University of Incarnate Word, School of Pharmacy, San Antonio, Texas

Abstract

Bile duct ligation (BDL), a model of hepatic cirrhosis, is associated with dilutional hyponatremia and inappropriate vasopressin release. ΔFosB staining was significantly increased in vasopressin and oxytocin magnocellular neurosecretory cells in the supraoptic nucleus (SON) of BDL rats. We tested the role of SON ΔFosB in fluid retention following BDL by injecting the SON ( n = 10) with 400 nl of an adeno-associated virus (AAV) vector expressing ΔJunD (a dominant negative construct for ΔFosB) plus green fluorescent protein (GFP) (AAV-GFP-ΔJunD). Controls were either noninjected or injected with an AAV vector expressing only GFP. Three weeks after BDL or sham ligation surgery, rats were individually housed in metabolism cages for 1 wk. Average daily water intake was significantly elevated in all BDL rats compared with sham ligated controls. Average daily urine output was significantly greater in AAV-GFP-ΔJunD-treated BDL rats compared with all other groups. Daily average urine sodium concentration was significantly lower in AAV-GFP-ΔJunD-treated BDL rats than the other groups, although average daily sodium excretion was not different among the groups. SON expression of ΔJunD produced a diuresis in BDL rats that may be related to decreased circulating levels of vasopressin or oxytocin. These findings support the view that ΔFosB expression in SON magnocellular secretory cells contribute to dilutional hyponatremia in BDL rats.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

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