PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE - A NEUROPEPTIDE WITH POTENT INOTROPIC AND CORONARY VASODILATORY EFFECTS IN NEONATAL PIGHEARTS

Cardiac effects of the neuropeptide pituitary adenylate cyclase activa ting polypeptide (PACAP) have not previously been reported. We investi gated the influence of PACAP, vasoactive intestinal polypeptide (68% h omology with PACAP) and the beta-adrenergic receptor agonist isoproter enol on contractile function and coronary vascular tone in isolated pi glet hearts (1 to 5 d of age). Paced (180 beats/min) isovolumically be ating hearts underwent retrograde aortic perfusion at constant coronar y flow (approximately 3 mL.min-1.g-1) with an erythrocyte-enriched (he matocrit 15 to 20%) solution (37-degrees-C). Agonists were injected in to the aortic root of hearts, and the positive (+) and negative (-) ch anges in maximum rate of change of systolic pressure with respect to t ime (dP/dt(max)) and in coronary perfusion pressure (that reflected al terations in vascular tone) were measured. PACAP (n = 8, 0.1 and 0.5 n mol) increased (+) dP/dt(max) from 944 +/- 59 to 1519 +/- 206 mm Hg/s and from 867 +/- 40 to 2010 +/- 226 mm Hg/s (p < 0.05); increased (-) dP/dt(max) from 1114 +/- 41 to 1439 +/-95 mm Hg and from 999 +/- 37 to 1668 +/- 145 nun Hg/s (p < 0.05); and decreased perfusion pressure fr om 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 intestin al polypeptide (n = 6, 0.1 and 0.5 nmol) increased (+) dP/dt(max) from 767 +/- 53 to 806 +/- 37 mm Hg/s and from 829 +/- 94 to 942 +/- 85 mm Hg/s (NS); increased (-) dP/dt(max) from 883 +/- 73 to 926 +/- 45 mm Hg/s and from 923 +/- 82 to 1054 +/- 78 mm Hg/s (NS); and decreased pe rfusion 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). Isoprotereno l (n = 5, 0.1 and 0.5 nmol) increased (+) dP/dt(max) from 793 +/- 51 t o 1343 +/- 75 mm Hg/s (p = 0.09) and from 825 +/- 38 to 2275 +/- 275 m m Hg/s (p < 0.05); increased (-) dP/dt(max) from 977 +/- 56 to 1314 +/ - 66 mm Hg/s and from 865 +/- 35 to 1738 +/- 143 mm Hg/s (p < 0.05); a nd decreased perfusion pressure from 58.8 +/- 2.2 to 51.6 +/- 2.3 mm H g and from 64 +/- 2.3 to 49.8 +/- 2.9 mm Hg, respectively (p < 0.05). In summary, PACAP produced positive inotropic, luisitropic, and corona ry vasodilatory effects, in piglet hearts, which may make PACAP a prom ising cardiotonic agent for the treatment of neonates with myocardial contractile dysfunction.