Effects of Bile Duct Ligation (BDL) and Enalapril on Angiotensin receptors in the Subfornical Organ (SFO) in Rats

Abstract

Inappropriate vasopressin (AVP) release causes fluid retention, ascites, and dilutional hyponatremia associated with cirrhosis. Although the central molecular mechanisms that mediate inappropriate AVP release are not clear, plasma angiotensin II (AngII) has been implicated as a factor in the pathogenesis of dilutional hyponatremia. To better understand the relationship between the CNS effects of circulating AngII and increased AVP release during cirrhosis, we examined the effects of BDL with treatment of enalapril on AT1R expression in the SFO. Starting the 21st day after BDL surgery BDL rats were either treated with enalapril dissolved in tap water (0.25mg/mL) or with normal tap water. On the 28th day (after 7 days of enalapril treatment), the rats were anesthetized, decapitated and brain punches were taken of the SFO for quantification of AT1R. Western Blot analysis showed an increase in AT1R in the SFO of untreated BDL rats as compared to sham ligated controls. In enalapril treated BDL rats, AT1R decreased compared to drug naïve BDL rats. Plasma osmolality and hematocrit also showed a trend towards normalization in enalapril treated BDL rats. These results are consistent with the hypothesis that AngII may increase excitatory drive in the SFO through upregulation of its AT1R thus leading to a decompensation of sodium balance and hyponatremia. (R01 HL062576)