An evaluation of the efficacy of vasoactive intestinal polypeptide antagonists in vivo in the anaesthetized dog.

The effectiveness of competitive peptide vasoactive intestinal polypeptide (VIP) receptor antagonists was evaluated on heart rate in the anaesthetized dog. Two specific antagonists, VIP (6-28) and [D-p-Cl-Phe(6), Leu(17)]-VIP, and a nonspecific antagonist, pituitary adenylate cyclase activating peptide fragment (6-27) (PACAP), were studied. VIP (6-28) and [D-p-Cl-Phe(6), Leu(17)]-VIP (100 microg i.c.) increased the heart rate, whereas PACAP (100 microg i.c.) reduced the baseline heart rate. All three shifted the VIP dose-response curve to the right by two- to threefold for 30 min. In conclusion, PACAP, VIP (6-28), and [D-p-Cl-Phe(6), Leu(17)]-VIP have a direct effect on the heart rate, are equally effective, and the effects last approximately 30 min in vivo. Copyright 2002 S. Karger AG, Basel