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 mug i.c.) increased the heart rate, whereas PACAP (100 mug 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 (C) 2002 S. Karger AG, Basel.