Dilutional hyponatremia associated with liver cirrhosis is due to inappropriate release of arginine vasopressin (AVP). Elevated plasma AVP causes water retention resulting in a decrease in plasma osmolality. Cirrhosis, in this study caused by ligation of the common bile duct (BDL), leads to a decrease in central vascular blood volume and hypotension, stimuli for non-osmotic AVP release. The A1/A2 neurons stimulate the release of AVP from the supraoptic nucleus (SON) in response to non-osmotic stimuli. We hypothesize that the A1/A2 noradrenergic neurons support chronic release of AVP in cirrhosis leading to dilutional hyponatremia. Adult, male rats were anesthetized with 2-3% isoflurane (mixed with 95% O2/5% CO2) and injected in the SON with anti-DBH saporin (DSAP) or vehicle followed by either BDL or sham surgery. Plasma copeptin, osmolality, and hematocrit were measured. Brains were processed for delta FosB, dopamine β-hydroxylase (DBH) and AVP immunohistochemistry. DSAP injection: i) significantly reduced the number of DBH immunoreactive A1/A2 neurons (A1, P<0.0001; A2, P=0.0014), ii) significantly reduced the number of A1/A2 neurons immunoreactive to both DBH and delta FosB positive neurons (A1, P=0.0015; A2, P<0.0001), iii) reduced the number of SON neurons immunoreactive to both AVP and delta FosB (P<0.0001), iv) prevented the increase in plasma copeptin observed in vehicle injected BDL rats (P=0.0011) and v) normalized plasma osmolality and hematocrit (plasma osmolality, P =0.0475; hematocrit, P = 0.0051) as compared to vehicle injection. Our data suggest that A1/A2 neurons contribute to increased plasma copeptin and hypoosmolality in male BDL rats.
Arginine vasopressin (AVP) and oxytocin (OXY) are released by magnocellular neurosecretory cells that project to the posterior pituitary. While AVP and OXY currently receive more attention for their contributions to affiliative behavior, this mini-review discusses their roles in cardiovascular function broadly defined to include indirect effects that influence cardiovascular function. The traditional view is that neither AVP nor OXY contributes to basal cardiovascular function, although some recent studies suggest that this position might be re-evaluated. More evidence indicates that adaptations and neuroplasticity of AVP and OXY neurons contribute to cardiovascular pathophysiology.
Purpose Inappropriate release of arginine vasopressin (AVP) has been linked to dilutional hyponatremia in patients with liver disease. Plasma AVP remains elevated leading to 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 increased plasma AVP and dilutional hyponatremia. Method We used the Bile duct ligation (BDL) rat model of liver failure for our experiments. 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 plasma AVP using ELISA. Plasma osmolality and hematocrit measurements were also taken. Immunohistochemistry for delta fosB and dopamine beta‐hydroxylase (DβH) was performed on brain tissue slices. The slices were viewed using an Olympus microscope (BX41) equipped for epifluorescence and images were taken using Olympus DP70 digital camera with DP manager software (version 2.2.1). The number of immunoreactive cells to ΔFosB and DβH were counted using Image J. Results We found that lesioning of the A1/A2 neurons in the Saporin/BDL group (n=9) caused a decrease in the plasma AVP concentration versus the Vehicle/BDL control group (n=6), p<0.05. However, the number of delta fosB immunoreactive A1/A2 cells was not significantly different. Lesioning of the A1/A2 neurons seemed to normalize osmolality and hematocrit in the BDL group. Although the difference was not statistically significant. Conclusion Our experiments suggests that A1/A2 neurons could be involved in the increased plasma AVP seen in male BDL rats as well as the decreased plasma osmolality.
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