Pituitary Adenylate Cyclase-Activating Polypeptide Dilates Cerebral Arterioles of Newborn Pigs

Abstract

Abstract

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 periarach-noid 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.