Vasoactive intestinal peptide down-regulates the intrahepatic renin-angiotensin system in the anaesthetized rat.

Gastric sodium loading results in an increase in the portal venous concentration of vasoactive intestinal peptide (VIP) and down-regulation of both the intrahepatic and circulating renin-angiotensin systems. In the present study we sought to determine whether an increase in the concentration of VIP in the portal circulation might act to down-regulate the intrahepatic and/or circulating renin-angiotensin systems. Male Sprague-Dawley rats were infused intraportally with haemaccel vehicle or VIP in haemaccel for 60 min. Livers were harvested and blood was sampled. Angiotensin-converting enzyme (ACE) activity and angiotensinogen, angiotensin I, angiotensin II and renin concentrations were measured. VIP infusion decreased hepatic ACE activity (P < 0.05), the hepatic angiotensinogen concentration (P < 0.001) and the hepatic angiotensin I concentration (P < 0.05). The plasma angiotensinogen concentration and serum ACE activity were also decreased by intraportal VIP infusion (P < 0.05 for each). Plasma renin, angiotensin I and angiotensin II concentrations were unchanged by VIP infusion. We conclude that an increase in the portal venous VIP concentration down-regulates the intrahepatic renin-angiotensin system. These changes are similar to those reported after gastric sodium loading, and we suggest, therefore, that the increase in portal venous VIP that occurs after gastric sodium is the means by which the gastric sodium sensor signals the liver to effect these changes in the renin-angiotensin system.