Ishizuka O, Hosono M, Nakamura K
Research Laboratories, Pharmaceuticals Group, Nippon Kayaku, Tokyo, Japan.
J Cardiovasc Pharmacol. 1992 Aug;20(2):261-7. doi: 10.1097/00005344-199208000-00011.
Cardiac and coronary vasodilator effects of NKH477, a novel water-soluble forskolin derivative, and isoproterenol, a nonselective beta-adrenoceptor full agonist, were compared in isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. Both agents were injected intraarterially. The two agents increased the force of contraction of the paced papillary muscle and of the unpaced muscle, and the rate of automaticity of the latter. They increased sinus rate and accelerated AV nodal conduction. In producing these cardiac effects, both agents were similar, although NKH477 was 120-350 times less potent than isoproterenol; however, NKH477 differed distinctly from isoproterenol in that the former increased coronary blood flow more greatly than the latter. Thus, NKH477 is more coronary vasodilatory than positive inotropic, and more positive inotropic than positive chronotropic. Such a cardiovascular profile of NKH477 was similar to that of forskolin, except for the duration of actions; NKH477 was longer-acting than forskolin.
在犬离体血液灌注乳头肌、窦房（SA）结和房室（AV）结标本中，比较了新型水溶性福司可林衍生物NKH477与非选择性β肾上腺素能受体完全激动剂异丙肾上腺素的心脏和冠状血管舒张作用。两种药物均经动脉注射。两种药物均增加了起搏乳头肌和非起搏乳头肌的收缩力以及后者的自律性。它们增加窦性心率并加速房室结传导。在产生这些心脏效应方面，两种药物相似，尽管NKH477的效力比异丙肾上腺素低120 - 350倍；然而，NKH477与异丙肾上腺素明显不同，前者比后者更能显著增加冠状动脉血流量。因此，NKH477的冠状动脉舒张作用强于正性肌力作用，正性肌力作用强于正性变时作用。除作用持续时间外，NKH477的这种心血管特性与福司可林相似；NKH477的作用持续时间比福司可林更长。
