ANALYSIS OF RESPONSES TO PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE-38 IN THE FELINE HINDQUARTERS VASCULAR BED

Responses to pituitary adenylate cyclase activating polypeptide (PACAP )-38 were investigated and compared with responses to PACAP-27 and vas oactive intestinal polypeptide (VIP) in the hindquarters vascular bed of the cat under constant flow conditions. Injections of PACAP-38 into the hindquarters perfusion circuit caused dose-related, biphasic chan ges characterized by initial decreases followed by increases in both h indquarters perfusion and systemic arterial pressure. In relative term s, PACAP-38 was less potent then PACAP-27 and VIP in dilating the hind quarters vascular bed, with the order of related potency being VIP > P ACAP-27 > PACAP-38 when the doses required to decrease hindquarters pe rfusion pressure by 25 mm Hg were compared. When comparing the relativ e vasoconstrictor activity of PACAP-38 to that of PACAP-27 and norepin ephrine, PACAP-38 was approximately 3-fold less potent than PACAP-27 a nd 10-fold less potent than norepinephrine. The vasoconstrictor compon ent of the response to PACAP-38 and, as shown previously, for PACAP-27 was blocked by phentolamine in a dose that significantly reduced pres sor responses to norepinephrine in the hindquarters vascular bed. The present data show that PACAP-38 has significant vasodilator and vasoco nstrictor activity in the hindquarters vascular bed of the cat, and th at the 27 amino acid form of the peptide has greater depressor and pre ssor activity than PACAP-38.