Bile Duct Ligation Differently Effects Plasma Osmolality but not Blood Pressure in Male vs Female Rats

Abstract

Dilutional hyponatremia is known to increase morbidity in patients with advanced liver disease due to the inappropriate release of arginine vasopressin (AVP). Our previous studies show that bile duct ligation (BDL), an animal model of liver disease, increase circulating copeptin in male rats but a decrease in osmolality as compared to the shams. Female BDL rats did not demonstrate the same increase in circulating copeptin or decrease in plasma osmolality as compared to sham females. In this study, we tested if male and female BDL rats showed differences in their blood pressure responses to BDL. Previous studies indicate that male BDL rats become hypotensive while females have not been tested. Adult male and female Sprague Dawley rats had either BDL or sham ligation surgery and were implanted with radio telemetry transmitters for measuring Mean arterial pressure (MAP) and heart rates (HR). Rats were housed in a commercial metabolic cage for one week prior to euthanasian to measure water intake and urine output. No change was seen in daily water intake between the male BDL and sham groups, however the female BDL animals had a significant increase in their daily water intake (p < 0.05, n =6) when compared to the shams. Despite the increase in water intake seen only in BDL females, both the male and female BDL groups saw a large increase in daily urine output (p < 0.001, n = 4‐9) compared to the shams. Analysis of variance showed that there was a main effect of treatment (F(3, 20)= 6.7, P < 0.05) that was due to the MAP of both male and female BDL groups being significantly lower than female shams (P < 0.05). Heart rate was not different among either sexes or treatment groups. Liver weight to body weight ratio was significantly increased in both male and female BDL rats. These results show that both male and female BDL rats became hypotensive when compared to their shams, however the differences in development of hyponatremia among the male and female rats are not due to difference in blood pressure changes associated with BDL.