title: VIP and PACAP display different vasodilatory effects in rabbit coronary and cerebral arteries.
abstract: Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are closely related peptides with wide distribution in the nervous system. The aim of the present study was to investigate functional characteristics and the influence of sex steroids on the vasodilatory effects of these two peptides in cerebral and coronary vessels from female New Zealand White (NZW) rabbits. The localization and concentration of VIP and PACAP in cardiovascular tissue was evaluated using immunohistochemistry and radioimmunoassays. The vasodilatory effects of VIP and PACAP were investigated using myographs, allowing isometric tension recordings. In order to evaluate the influence of steroid hormones, the rabbits were ovariectomized and randomized to treatment for 4 weeks with 17beta-estradiol (E(2)), Norethindrone Acetate (NETA), E(2)+NETA or placebo. Ring segments of the posterior cerebral artery, the right proximal coronary artery and the distal left coronary artery were examined. The highest concentrations of VIP/PACAP were observed in cerebral and coronary arteries: 5.0/5.7 and 2.8/3.5 pmol/g, respectively. The peptides were localized in nerve fibres innervating the arteries. Both peptides produced dose-dependent vasodilatory responses in all vessels investigated. While the effects of PACAP were identical in cerebral and coronary arterial segments, the effects of VIP displayed significant differences (E(max), pI(2), Hill-slope). Treatment with sex steroids induced no changes in the vascular effects of the two peptides. These results indicate different mechanisms of action for the vasodilating effects of the two closely related peptides VIP and PACAP in different areas of the coronary and cerebrovascular tree. Treatment with female sex steroids does not seem to change these mechanisms.
authors.affiliation: Department of Obstetrics and Gynaecology 537, Hvidovre University Hospital, Kettegård Allé 30, DK-2650 Hvidovre, Copenhagen, Denmark. torur.dalsgaard@dadlnet.dk
authors.forename: Tórur
authors.initials: T
authors.lastname: Dalsgaard
authors.forename: Jens
authors.initials: J
authors.lastname: Hannibal
authors.forename: Jan
authors.initials: J
authors.lastname: Fahrenkrug
authors.forename: Christian Rifbjerg
authors.initials: CR
authors.lastname: Larsen
authors.forename: Bent
authors.initials: B
authors.lastname: Ottesen
mesh_terms: D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011817:Rabbits; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide