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 vasoactive 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 changes characterized by initial decreases followed by increases in both hindquarters perfusion and systemic arterial pressure. In relative terms, PACAP-38 was less potent then PACAP-27 and VIP in dilating the hindquarters vascular bed, with the order of related potency being VIP > PACAP-27 > PACAP-38 when the doses required to decrease hindquarters perfusion pressure by 25 mm Hg were compared. When comparing the relative vasoconstrictor activity of PACAP-38 to that of PACAP-27 and norepinephrine, PACAP-38 was approximately 3-fold less potent than PACAP-27 and 10-fold less potent than norepinephrine. The vasoconstrictor component of the response to PACAP-38 and, as shown previously, for PACAP-27 was blocked by phentolamine in a dose that significantly reduced pressor responses to norepinephrine in the hindquarters vascular bed. The present data show that PACAP-38 has significant vasodilator and vasoconstrictor activity in the hindquarters vascular bed of the cat, and that the 27 amino acid form of the peptide has greater depressor and pressor activity than PACAP-38.