CONTRACTILE AND CORONARY VASCULAR EFFECTS OF PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE IN NEONATAL PIG HEARTS

Objective: The purpose was to investigate the influence of the 38-amin o-acid neuropeptide, pituitary adenylate cyclase activating polypeptid e (PACAP(38)), on contractile function and coronary vascular tone in n eonatal hearts. Methods: Isolated, paced (150 bpm), isovolumically-bea ting, piglet hearts (n = 19) underwent retrograde aortic perfusion at constant coronary flow (approximate to 2.5 ml/min/g(wet)) with an eryt hrocyte-enriched (Hct 15-20%) solution (37 degrees C). Agonists were i njected into the aortic root of hearts, and the changes in +dP/dt(max) and -dP/dt(max) (reflecting contractility), and coronary perfusion pr essure (reflecting vascular tone) were determined. Responses to PAPCAP (38) were compared to isoproterenol, and to the truncated peptide PACA P(6-38). Results: PACAP(38) (0.1 and 0.5 nmol) increased +dP/dt(max) f rom 1387.4 +/- 134.6 to 1619.0 +/- 118.7, and from 1296.2 +/- 93.4 to 1872.2 +/- 111.4 mmHg/s (P < 0.05); changed -dP/dt(max) from -1087.6 /- 107.5 to -1206.6 +/- 93.6, and from -1025.0 +/- 46.8 to -1375.4 +/- 80.9 mmHg/s (P < 0.05) and decreased coronary perfusion pressure from 61.8 +/- 2.5 to 51.0 +/- 3.8, and from 62.5 +/- 1.0 to 45.3 +/- 3.3 m mHg (P < 0.05), respectively. In comparison, isoproterenol (0.1 nmol) increased +dP/dt(max) from 1313.6 +/- 62.8 to 1679.0 +/- 74.4 (P < 0.0 5), and -dP/dt(max) from -1026.4 +/- 54.1 to -1222.6 +/- 57.4 mmHg/s ( P < 0.05). PACAP(6-38) reduced PACAP(38)'s coronary vasodilatory, but not its contractile, effect. When compared to our previous studies of the the 27-amino-acid neuropeptide PACAP(27), PACAP(38) had less poten t contractile, but similar vasodilatory effects, Conclusions: PACAP(38 ) enhanced contractility and produced coronary vasodilation in piglet hearts, which may make PACAP(38) a promising cardiotonic agent for the treatment of neonates with heart failure.