Role of A1/A2 Neurons in Increased Vasopressin Release in Male Bile Duct Ligated Rats

Bile duct ligation (BDL), a rat model of liver failure causes increased vasopressin release leading to water retention and a decrease in plasma osmolality. Water retained in ascites leads to a perceived decrease in plasma volume by the A1/A2 norepinephrine neurons in the caudal ventrolateral medulla (CVLM) and the nucleus tractus solitarius (NTS) respectively, increasing vasopressin release. We hypothesized that lesioning norepinephrine A1/A2 neurons will prevent increased plasma vasopressin (measured as a function of plasma copeptin concentrations), normalize hematocrit and plasma osmolality, and decrease the number of immunoreactive ΔFosB and DβH cells in the NTS and CVLM. To investigate the role of A1/A2 neurons in the increase in vasopressin release observed in male BDL rats, anti-DβH-Saporin [IT-03] (Advanced Targeting Systems), or vehicle was injected into the SON. BDL surgery or sham surgery was performed after two weeks. Four weeks following the BDL/Sham surgery, the rats were sacrificed, and blood samples were taken for copeptin, hematocrit and plasma osmolality measurements. Hindbrains were processed for immunohistochemistry. The results showed a significant decrease in CVLM ΔFosB reactive cells in the Saporin/BDL group (n=2) as compared to the Vehicle/BDL group (n=3) (p< 0.001). DβH immunoreactive cells in both the CVLM and NTS were significantly decreased in the Saporin/BDL group as compared to the vehicle/BDL group (p< 0.001). However, differences were not observed for the copeptin concentration, hematocrit and plasma osmolality. The results suggest that lesions of SON-projecting A1/A2 neurons may not be sufficient to prevent vasopressin release associated with BDL.