Phosphodiesterase inhibition and positive inotropic effects.
Phosphodiesterase inhibition and positive inotropic effects.
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磷酸二酯酶抑制和正性肌力作用。
DOI：
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发表时间：
1989
影响因子：
3
通讯作者：
H. Scholz
中科院分区：
文献类型：
--
作者：
W. Schmitz;H. E. von der Leyen;W. Meyer;J. Neumann;H. Scholz
许多新开发的正性肌力药物是磷酸二酯酶抑制剂。在心脏中至少分离出四种磷酸二酯酶（PDE I-IV）。根据所研究的物种，PDE 抑制剂的正性肌力作用似乎与可溶性或颗粒 PDE III 或与肌浆网结合的颗粒 PDE 的抑制相关。在从患有特发性扩张型心肌病导致的终末期心力衰竭的心脏中分离出的人心室组织中，与健康对照相比，磷酸二酯酶抑制剂的正性肌力作用大大降低。这不能用 PDE 敏感性受损来解释，因为健康心脏和患病心脏中的 PDE 抑制剂都类似地抑制 PDE。然而，由于正性肌力作用的降低伴随着细胞cAMP浓度增加的减少，因此可能涉及腺苷酸环化酶形成的cAMP受损。腺苷酸环化酶活性受损可能是由于最近在衰竭心脏中观察到的抑制性 GTP 结合蛋白（Gi 蛋白）增加所致。
Many newly developed positive inotropic agents are phosphodiesterase inhibitors. In the heart at least four phosphodiesterases (PDE I-IV) have been isolated. Depending on the species investigated, the positive inotropic effects of the PDE inhibitors appear to be correlated to the inhibition of a soluble or particulate PDE III or to a particulate PDE bound to the sarcoplasmic reticulum. In human ventricular tissue isolated from hearts with end-stage heart failure due to idiopathic dilated cardiomyopathy the positive inotropic effect of phosphodiesterase inhibitors is greatly reduced compared to healthy controls. This cannot be explained by an impaired sensitivity of the PDEs because the PDEs were similarly inhibited by PDE inhibitors in both healthy and diseased hearts. However, because the reduced positive inotropic effect is accompanied by a reduced increase in cellular cAMP concentration, an impaired formation of cAMP by the adenylate cyclase is probably involved. The impaired adenylate cyclase activity can result from an increased inhibitory GTP-binding protein (Gi-protein) recently observed in failing hearts.