Role of A1/A2 Neurons in the Dysregulation of Vasopressin Release and Dilutional Hyponatremia in Liver Disease
dc.creator | Aikins, Ato | |
dc.creator | Little, Joel | |
dc.creator | Cunningham, Joseph | |
dc.creator.orcid | 0000-0001-8936-1053 (Aikins, Ato) | |
dc.date.accessioned | 2021-04-30T17:39:33Z | |
dc.date.available | 2021-04-30T17:39:33Z | |
dc.date.issued | 2021 | |
dc.description.abstract | Abstract Purpose: Inappropriate release of arginine vasopressin (AVP) has been linked to dilutional hyponatremia in patients with cirrhosis. Elevated Plasma AVP causes water retention, hypoosmolality, ascites formation, and a perceived decrease in plasma volume. The perceived decrease in plasma volume is sensed by the A1/A2 norepinephrine neurons in the caudal ventrolateral medulla (CVLM) and the nucleus tractus solitarius (NTS) respectively. We propose that these neurons provide the initial stimuli that activates AVP-secreting neurons in the supraoptic nucleus (SON) leading to inappropriate AVP release and dilutional hyponatremia. Method: Adult male rats were bile duct ligated (BDL) to model cirrhosis. Selective lesioning of the SON-projecting A1/A2 norepinephrine neurons was achieved using anti-DβH-Saporin [IT-03] (Advanced Targeting Systems). Plasma copeptin concentration was measured as a surrogate marker for AVP using ELISA. Plasma osmolality and hematocrit measurements were also taken. Immunohistochemistry for delta FosB and dopamine beta-hydroxylase (DβH) was performed on brain slices. Results: Lesions of the A1/A2 neurons projecting to SON (Saporin/BDL n=9) was associated with decreased copeptin as compared to BDL controls (Vehicle/BDL, n=6, p< 0.05). However, the number of delta FosB immunoreactive A1/A2 cells was not significantly different. While A1/A2 lesions seemed to normalize osmolality and hematocrit in the BDL rats, the trends were not statistically significant. Conclusion: The result suggests that A1/A2 neurons could contribute to increased plasma AVP seen in male BDL rats, but there could be other contributing factors preventing a recovery of plasma osmolality. | |
dc.description.sponsorship | R01 HL142341 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12503/30600 | |
dc.language.iso | en | |
dc.title | Role of A1/A2 Neurons in the Dysregulation of Vasopressin Release and Dilutional Hyponatremia in Liver Disease | |
dc.type | presentation | |
dc.type.material | text |