Abstract
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 β-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°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. In comparison, vasoactive intestinal polypeptide (n = 6, 0.1 and 0.5 nmol) increased (+) dP/dtmax from 767 ± 53 to 806 ± 37 mm Hg/s and from 829 ± 94 to 942 ± 85 mm Hg/s (NS); increased (-) dP/dtmax from 883 ± 73 to 926 ± 45 mm Hg/s and from 923 ± 82 to 1054 ± 78 mm Hg/s (NS); and decreased perfusion pressure from 57.9 ± 4.9 to 50.0 ± 3.6 mm Hg and from 59.0 ± 4.3 to 44.6 ± 3.8 mm Hg, respectively (p < 0.05). Isoproterenol (n = 5, 0.1 and 0.5 nmol) increased (+) dP/dtmax from 793 ± 51 to 1343 ± 75 mm Hg/s (p = 0.09) and from 825 ± 38 to 2275 ± 275 mm Hg/s (p < 0.05); increased (-) dP/dtmax from 977 ± 56 to 1314 ± 66 mm Hg/s and from 865 ± 35 to 1738 ± 143 mm Hg/s (p < 0.05); and decreased perfusion pressure from 58.8 ± 2.2 to 51.6 ± 2.3 mm Hg and from 64 ± 2.3 to 49.8 ± 2.9 mm Hg, respectively (p < 0.05). In summary, PACAP produced positive inotropic, luisitropic, and coronary vasodilatory effects in piglet hearts, which may make PACAP a promising cardiotonic agent for the treatment of neonates with myocardial contractile dysfunction.
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Ross-Ascuitto, N., Ascuitto, R., Ramage, D. et al. Pituitary Adenylate Cyclase Activating Polypeptide: A Neuropeptide with Potent Inotropic and Coronary Vasodilatory Effects in Neonatal Pig Hearts. Pediatr Res 34, 323–328 (1993). https://doi.org/10.1203/00006450-199309000-00017
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DOI: https://doi.org/10.1203/00006450-199309000-00017
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