Sex Difference and Hormones in the Regulation of Vasopressin Secretion during Dilutional Hyponatremia
Authors: Balapattabi Kirthikaa , Little Joel T , Bachelor Martha E , Cunningham Rebecca L , Cunningham J. Thomas 
Published: June 2021

Dilutional hyponatremia due to elevated arginine vasopressin (AVP) secretion increases mortality in patients with liver failure. No previous studies have addressed sex difference in dilutional hyponatremia in animal models of liver failure. The aim of this study is to investigate sex difference in dilutional hyponatremia and the effect of ovarian hormones in AVP secretion. We have used chronic bile duct ligated (BDL) rats, a model of dilutional hyponatremia associated with liver failure.

Adult male Sprague Dawley rats, female Sprague Dawley rats and ovariectomized (OVX) female rats were used. After two weeks, the rats had BDL or sham ligation surgery. Four weeks later, the brains were processed for immunohistochemistry analysis of FosB and AVP expression. Blood samples were collected to measure plasma osmolality, hematocrit, circulating estradiol and copeptin concentration. Copeptin was used as biomarker for plasma AVP. Liver weight, body weight, and fluid accumulation were recorded to verify if the rats developed liver failure and ascites. Data were analyzed by one ANOVA with Bonferroni post hoc comparisons.

All the BDL rats had significant increase in liver to body weight ratio compared to sham rats indicating liver failure and ascites with bile duct ligation. Male BDL rats had hyponatremia along with significant increases in plasma copeptin and FosB expression in Supraoptic AVP neurons compared to male shams (all p<0.05; 5–7). Unlike male BDL rats, the female BDL rats did not become hyponatremia and did not had increases Supraoptic AVP neuron activation and copeptin secretion compared to female sham.

Ovariectomy significantly decreased plasma estradiol concentration in sham rats compared to intact female sham (p< 0.05; 6–10). However, circulating estradiol concentration was significantly elevated in ovariectomized BDL (OVX BDL) rats compared to the ovariectomized sham (OVX sham) and female sham rats (p<0.05; 6–10). To identify the source of estradiol contributing to the observed increase in OVX BDL rats, adrenal glands were collected at the end of protocol. Adrenal gland steroids were extracted to measure estradiol and its precursors, testosterone and DHEA concentration.

The OVX BDL rats had significantly increased adrenal estradiol along with significant decrease in adrenal testosterone and DHEA compared to OVX sham rats (all p< 0.05; 6–7). Plasma osmolality, hematocrit and copeptin concentration were not different between OVX BDL and OVX sham rats. Our results show that unlike male BDL rats, female BDL rats did not develop hyponatremia, supraoptic AVP neuron activation, or increased copeptin secretion compared to sham ligated females. Female OVX BDL rats did not become hyponatremia or increased copeptin secretion compared to female OVX sham rats. It is possible that the increase in adrenal estradiol compensated for the lack of ovarian estrogens in OVX BDL rats. Additional experiments will be required to determine the effects of estrogen in this model.

Support or Funding Information

Supported by R01 HL119458 and 18PRE34060035

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.