Ogino K, Burkhoff D, Bilezikian J P
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Endocrinology. 1995 Jul;136(7):3024-30. doi: 10.1210/endo.136.7.7789328.
PTH and PTH-related protein (PTHrP) have been regarded to have positive inotropic effects on the heart as well as positive chronotropic and vasodilator effects. However, inotropy due to a direct effect of these peptides has not heretofore been distinguished from an indirect inotropic effect as a result of altered heart rate or coronary flow. The aim of this study was to determine whether PTH and PTHrP have direct inotropic effects in isolated perfused rat hearts. Three groups of hearts were studied; in all groups, hearts contracted isovolumically and were perfused with a constant coronary pressure. In the control group, heart rate, coronary flow, peak pressure (LVPmax), peak rate of rise of LV pressure (dP/dtmax), and peak intracellular calcium (measured by aequorin) all increased with PTH and PTHrP in a dose-dependent manner. When heart rate was fixed by pacing in a second group of rats, PTH and PTHrP increased coronary flow, LVPmax, and dP/dtmax significantly, indicating that inotropic actions were not mediated solely by chronotropic effects. However, when heart rate was fixed by pacing and, additionally, coronary flow was held constant (by maximal prevasodilation with nitroprusside) in a third group of rats, there was no significant effect of either PTH or PTHrP on LVPmax, dP/dtmax, or peak intracellular calcium. To demonstrate the responsiveness of this latter preparation to inotropic stimulation, the beta-adrenergic agonist, isoproterenol, increased LVPmax, dP/dtmax, and peak calcium even when heart rate was fixed and vasodilation was maximal. Thus, PTH and PTHrP are inotropic agents by virtue of their influence on coronary flow and heart rate, but not by any direct effect on contractile elements in the heart.
甲状旁腺激素（PTH）和甲状旁腺激素相关蛋白（PTHrP）被认为对心脏具有正性肌力作用，以及正性变时和血管舒张作用。然而，迄今为止，这些肽的直接作用导致的心肌收缩力增强尚未与心率或冠状动脉血流改变引起的间接正性肌力作用区分开来。本研究的目的是确定PTH和PTHrP在离体灌注大鼠心脏中是否具有直接正性肌力作用。研究了三组心脏；在所有组中，心脏进行等容收缩，并在恒定的冠状动脉压力下灌注。在对照组中，心率、冠状动脉血流、峰值压力（左心室收缩压最大值，LVPmax）、左心室压力上升的峰值速率（dP/dtmax）和细胞内钙峰值（通过水母发光蛋白测量）均随PTH和PTHrP呈剂量依赖性增加。在第二组大鼠中通过起搏固定心率时，PTH和PTHrP显著增加冠状动脉血流、LVPmax和dP/dtmax，表明正性肌力作用并非仅由变时作用介导。然而，在第三组大鼠中通过起搏固定心率并额外使冠状动脉血流保持恒定（通过硝普钠进行最大程度的血管舒张）时，PTH或PTHrP对LVPmax、dP/dtmax或细胞内钙峰值均无显著影响。为了证明后一种制剂对正性肌力刺激的反应性，即使在心率固定且血管舒张最大时，β-肾上腺素能激动剂异丙肾上腺素也能增加LVPmax、dP/dtmax和钙峰值。因此，PTH和PTHrP是通过对冠状动脉血流和心率的影响而具有正性肌力作用的药物，而非对心脏收缩成分有任何直接作用。
