Pituitary adenylate cyclase activating polypeptide: a neuropeptide with potent inotropic and coronary vasodilatory effects in neonatal pig hearts.
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)
Ross-Ascuitto
N T
NT
Tulane University School of Medicine, Department of Pediatrics, New Orleans, Louisiana 70112.
Ascuitto
R J
RJ
Ramage
D
D
Kydon
D W
DW
Coy
D H
DH
Kadowitz
P J
PJ
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*
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