Lack of Hepatic Inactivation of Canine Vasoactive Intestinal Peptide

Abstract

To study hepatic inactivation of vasoactive intestinal peptide (VIP), in 3 dogs with gastric fistula the portal vein and inferior vena cava were transposed, thus allowing access to the portal vein through a hind leg vein. To demonstrate that the liver's ability to inactivate peptides was intact in these dogs, each experiment with VIP was preceded by an intraportal infusion of 4 μ kg-1 hr-1 of pentagastrin which failed to stimulate acid secretion. In the tests with VIP, a plateau of acid secretion was established by systemic venous infusion of 1 μg kg-1 hr-1 of pentagastrin. While continuing infusion of pentagastrin, 0.5, 1.0, or 2.0 μg kg-1 hr-1 of VIP was given by portal or systemic infusion for 30 min. VIP produced a dose-dependent decrease in acid secretion ranging from about 30% inhibition with the low dose to about 60% inhibition with the high dose. The degree of inhibition produced by portal infusion of VIP did not differ significantly from that produced by systemic infusion. After infusion of 30 μ kg-1 hr-1 of VIP for 5 min, peak serum VIP levels by radioimmunoassay were 769 ± 63 pmoles liter-1 after systemic and 717 ± 60 pmoles liter-1 after portal administration, an insignificant difference. After stopping the infusion the disappearance half-time of VIP was 3.1 ± 0.3 min and did not differ significantly with the two routes of administration. We conclude that inhibition of acid secretion and serum levels of VIP were not significantly different after portal or systemic infusions of VIP. Thus we found no evidence of selective hepatic inactivation of VIP in dogs.