Pituitary adenylate cyclase-activating polypeptide dilates cerebral arterioles of newborn pigs

The actions of the 38- and 27-amino acid forms of synthetic pituitary adenylate cyclase-activating polypeptide (PACAP-38 and PACAP-27) on cerebral arterioles were tested in anesthetized newborn pigs equipped with closed cranial windows. The diameter changes of pial arterioles to topical PACAP were measured and cortical periarachnoid cerebrospinal fluid samples were collected for measurement of cAMP. The 38- and 27-amino acid forms of PACAP produced similar dose-dependent vasodilations. The increases of pial arteriolar diameter produced by PACAP-38 were 6 +/- 1%, 15 +/- 2%, 23 +/- 3%, and 38 +/- 3%, and those produced by PACAP-27 were 6 +/- 1%, 15 +/- 2%, 27 +/- 5%, and 38 +/- 8% at 10((-9), 10(-8), 10(-7), and 10(-6) M, respectively. Arteriolar diameter began to increase 1-2 min and reached a maximum 6-8 min after topical application of PACAP. Vasoactive concentrations of PACAP-38 and PACAP-27 increased cerebrospinal fluid cAMP levels dose dependently. Thus, PACAP-38 and PACAP-27 appear to stimulate cerebral adenylate cyclase and are potent dilators of newborn pigs pial arterioles.