Vasoactive intestinal peptide (VIP) blood levels in cir-
Cirrhosis is associated with the development of carrhosis are elevated, but its hemodynamic and receptor diovascular abnormalities. The circulation becomes hycharacteristics remain unclarified. We aimed to quantify perkinetic with increases in cardiac output and VIP receptor characteristics in mesenteric arteries, splanchnic arterial blood flow and decreases in sysplasma VIP concentration by radioimmunoassay (RIA), temic vascular resistance and arterial pressure. The and the hemodynamic effects of VIP infusion in bile cause of these circulatory disturbances is unclear. It duct-ligated (BDL) cirrhotic and sham-operated control has been hypothesized that a circulating humoral facrats. Mesenteric arterial membranes were prepared by tor may be responsible. According to this hypothesis, a ultracentrifugation, and receptor characteristics were vasodilator substance normally produced in the gut studied using 125 I-labeled VIP as a radioligand. For the and inactivated in the liver would gain access to the hemodynamic study, there were four groups: cirrhotic and sham-operated rats were infused with either VIP systemic circulation, because of either shunting of (50 ng/kg/min for 15 minutes) or equivolumic isotonic blood through portosystemic collaterals or the inability saline. Regional blood flows were measured in conscious of the severely diseased liver to inactivate the subrats with radioactive microspheres. Receptor studies stance. Many such humoral factors have been proshowed high-and low-affinity binding sites for VIP, posed, including glucagon, 1,2 adenosine, 3,4 bile salts, 5,6 which had similar equilibrium dissociation constants prostaglandins, 7,8 nitric oxide, 9 and vasoactive intesti-(binding affinities) and receptor densities for both the nal peptide (VIP). Almost all of these substances have cirrhotic and control rats. Plasma VIP concentrations been subjected to intense study, with yet inconclusive were significantly elevated in the cirrhotic rats. In both results, except for VIP, which has generally received cirrhotic and sham-operated rats, VIP infusion prolittle attention. This is somewhat surprising because duced plasma levels approximately twofold to threefold increased over the basal levels observed in cirrhotic it is a known vasodilator, and VIP blood levels have rats. In cirrhotic rats, VIP infusion did not affect any been found in some studies to be elevated in patients hemodynamic parameter, whereas in the sham-operated and animal models with liver disease. 10-14 However, the rats VIP infusion significantly increased the mesenteric hemodynamic effects of VIP have not been well characvisceral blood flow. These results show that the hyporeterized, and details of VIP receptor characteristics have sponsiveness to VIP in cirrhotic rats is not attributable also heretofore not been studied. Therefore, our aims to receptor downregulation, implying postreceptor alin this study were to elucidate the hemodynamic effects terations. This suggests that VIP may not play a major of VIP and also to delineate its receptor characteristics role in the maintenance of splanchnic hyperemia in cirin a rat model of cirrhosis. Although use of a VIP antagrhosis. (HEPATOLOGY 1996;23:1174-1180.) onist would be preferable to delineate the pathophysiological role of VIP in cirrhosis, we chose instead to study VIP itself because of questions regarding the purity, effectiveness, and possible partial agonist activity