Changes in TRPV2 expression in paraventricular nucleus of bile duct ligated cirrhotic rats

Abstract

Inappropriate vasopressin (AVP) release, resulting in water retention and dilutional hyponatremia, contributes to the pathophysiology of hepatic cirrhosis. Chronic bile duct ligation (BDL), a commonly used model of hepatic cirrhosis is associated with elevated circulating AVP. We have observed that transient receptor potential vanilloid subtype 2 (TRPV2) is co-expressed with the magnocellular (MNC) AVP neurons in rats. However, the mechanisms responsible for inappropriate AVP release in hepatic cirrhosis have not yet been identified. This study test the hypothesis that changes in TRPV2 expression may be related to changes in osmosensitivity related to inappropriate AVP release. Four weeks after surgery, BDL rats demonstrated significantly increased plasma AVP, hypervolemia, and decreased plasma osmolality compared to sham ligated controls (SLC). Western Blot analysis revealed that TRPV2 expression was significantly increased in brain punches from BDL rats (n=8) containing the paraventricular nucleus (PVN) compared to the SLC (p<0.05; n=8). Densitometric measurements of the immunoreactive bands were normalized using actin. Our data suggests that increased TRPV2 expression in the MNC AVP neurons could alter their osmosensing ability resulting in increased AVP release during pathophysiological states involving hyponatremia and water retention.