Ascuitto R J, Ross-Ascuitto N T, Waddell A E, Kadowitz P J
Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Cardiovasc Res. 1996 Feb;31 Spec No:E153-9.
The purpose was to investigate the influence of the 38-amino-acid neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP38), on contractile function and coronary vascular tone in neonatal hearts.
Isolated, paced (150 bpm), isovolumically-beating, piglet hearts (n = 19) underwent retrograde aortic perfusion at constant coronary flow (approximately 2.5 ml/min/gwet) with an erythrocyte-enriched (Hct 15-20%) solution (37 degrees C). Agonists were injected into the aortic root of hearts, and the changes in +dP/dtmax and -dP/dtmax (reflecting contractility), and coronary perfusion pressure (reflecting vascular tone) were determined. Responses to PAPCAP38 were compared to isoproterenol, and to the truncated peptide PACAP6-38.
PACAP38 (0.1 and 0.5 nmol) increased +dP/dtmax from 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/dtmax 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 mmHg (P < 0.005), respectively. In comparison, isoproterenol (0.1 nmol) increased +dP/dtmax from 1313.6 +/- 62.8 to 1679.0 +/- 74.4 (P < 0.05), and -dP/dtmax from -1026.4 +/- 54.1 to -1222.6 +/- 57.4 mmHg/s (P < 0.05). PACAP6-38 reduced PACAP38's coronary vasodilatory, but not its contractile, effect. When compared to our previous studies of the 27-amino-acid neuropeptide PACAP27, PACAP38 had less potent contractile, but similar vasodilatory effects.
PACAP38 enhanced contractility and produced coronary vasodilation in piglet hearts, which may make PACAP38 a promising cardiotonic agent for the treatment of neonates with heart failure.
研究38个氨基酸的神经肽——垂体腺苷酸环化酶激活多肽（PACAP38）对新生仔猪心脏收缩功能和冠状血管张力的影响。
将离体、起搏（150次/分钟）、等容跳动的仔猪心脏（n = 19），在恒定冠状动脉血流（约2.5毫升/分钟/克湿重）下，用富含红细胞（血细胞比容15 - 20%）的溶液（37℃）进行逆行主动脉灌注。将激动剂注入心脏主动脉根部，测定+ dP/dtmax和 - dP/dtmax（反映收缩性）以及冠状动脉灌注压（反映血管张力）的变化。将对PAPCAP38的反应与异丙肾上腺素以及截短肽PACAP6 - 38进行比较。
PACAP38（0.1和0.5纳摩尔）使+ dP/dtmax分别从1387.4±134.6增加到1619.0±118.7，以及从1296.2±93.4增加到1872.2±111.4毫米汞柱/秒（P < 0.05）；使 - dP/dtmax分别从 - 1087.6±107.5变为 - 1206.6±93.6，以及从 - 1025.0±46.8变为 - 1375.4±80.9毫米汞柱/秒（P < 0.05），并使冠状动脉灌注压分别从61.8±2.5降至51.0±3.8，以及从62.5±1.0降至45.3±3.3毫米汞柱（P < 0.005）。相比之下，异丙肾上腺素（0.1纳摩尔）使+ dP/dtmax从1313.6±62.8增加到1679.0±74.4（P < 0.05），使 - dP/dtmax从 - 1026.4±54.1变为 - 1222.6±57.4毫米汞柱/秒（P < 0.05）。PACAP6 - 38减弱了PACAP38的冠状动脉舒张作用，但不影响其收缩作用。与我们之前对27个氨基酸的神经肽PACAP27的研究相比，PACAP38的收缩作用较弱，但血管舒张作用相似。
PACAP38增强了新生仔猪心脏的收缩性并引起冠状动脉舒张，这可能使PACAP38成为治疗新生儿心力衰竭的一种有前景的强心剂。
