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

Cunningham JT, Nedungadi TP, Walch JD, Nestler EJ, Gottlieb HB. Delta FosB in the supraoptic nucleus contributes to hyponatremia in rats with cirrhosis. Am J Physiol Regul Integr Comp Physiol 303: R177-R185, 2012. First published May 23, 2012; doi:10.1152/ajpregu.00142.2012.-Bile duct ligation (BDL), a model of hepatic cirrhosis, is associated with dilutional hyponatremia and inappropriate vasopressin release. Delta FosB 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 Delta FosB in fluid retention following BDL by injecting the SON (n = 10) with 400 nl of an adeno-associated virus (AAV) vector expressing Delta JunD (a dominant negative construct for Delta FosB) plus green fluorescent protein (GFP) (AAV-GFP- Delta JunD). 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-Delta JunD-treated BDL rats compared with all other groups. Daily average urine sodium concentration was significantly lower in AAV-GFP-Delta JunD-treated BDL rats than the other groups, although average daily sodium excretion was not different among the groups. SON expression of Delta JunD produced a diuresis in BDL rats that may be related to decreased circulating levels of vasopressin or oxytocin. These findings support the view that Delta FosB expression in SON magnocellular secretory cells contribute to dilutional hyponatremia in BDL rats.