title: Pituitary adenylate cyclase activating polypeptide: a neuropeptide with potent inotropic and coronary vasodilatory effects in neonatal pig hearts.
abstract: Cardiac effects of the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) have not previously been reported. We investigated the influence of PACAP, vasoactive intestinal polypeptide (68% homology with PACAP) and the beta-adrenergic receptor agonist isoproterenol on contractile function and coronary vascular tone in isolated piglet hearts (1 to 5 d of age). Paced (180 beats/min) isovolumically beating hearts underwent retrograde aortic perfusion at constant coronary flow (approximately 3 mL.min-1.g-1) with an erythrocyte-enriched (hematocrit 15 to 20%) solution (37 degrees C). Agonists were injected into the aortic root of hearts, and the positive (+) and negative (-) changes in maximum rate of change of systolic pressure with respect to time (dP/dtmax) and in coronary perfusion pressure (that reflected alterations in vascular tone) were measured. PACAP (n = 8, 0.1 and 0.5 nmol) increased (+) dP/dtmax from 944 +/- 59 to 1519 +/- 206 mm Hg/s and from 867 +/- 40 to 2010 +/- 226 mm Hg/s (p < 0.05); increased (-) dP/dtmax from 1114 +/- 41 to 1439 +/- 95 mm Hg and from 999 +/- 37 to 1668 +/- 145 mm Hg/s (p < 0.05); and decreased perfusion pressure from 61.4 +/- 3.1 to 48.9 +/- 2.3 mm Hg and from 60.5 +/- 2.4 to 43.9 +/- 2.3 mm Hg (p < 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Tulane University School of Medicine, Department of Pediatrics, New Orleans, Louisiana 70112.
authors.forename: N T
authors.initials: NT
authors.lastname: Ross-Ascuitto
authors.forename: R J
authors.initials: RJ
authors.lastname: Ascuitto
authors.forename: D
authors.initials: D
authors.lastname: Ramage
authors.forename: D W
authors.initials: DW
authors.lastname: Kydon
authors.forename: D H
authors.initials: DH
authors.lastname: Coy
authors.forename: P J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology*; D010477:Perfusion / Q000295:instrumentation; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013552:Swine; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014665:Vasodilator Agents; D014660:Vasoactive Intestinal Peptide; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine