Scholz H
Pharmakologisches Institut Universität, Universität-Krankenhaus Eppendorf, Hamburg.
Z Kardiol. 1994;83 Suppl 2:1-5.
A positive inotropic effect can be achieved by an increase in the intracellular concentration of calcium which interacts with the contractile proteins and/or by an increased sensitivity of the contractile proteins towards calcium. An increase in intracellular calcium concentration can be produced by cAMP-increasing agents. An increase in intracellular cAMP levels can result from stimulation of adenylate cyclase which leads to an increase in cAMP formation or from inhibition of the degradation of cAMP by inhibition of phosphodiesterases. The main effect of cAMP is to increase the calcium inward current during the action potential and to enhance the sequestration of calcium by intracellular calcium stores. This leads to an increase in calcium release and hence to an increase in the calcium concentration in the vicinity of the contractile proteins. PDE inhibitors are independent of receptors and also produce vasodilatation ("inodilators"). However, two potential disadvantages of PDEs must be kept in mind: 1) Positive chronotropy and induction of tachyarrhythmias and 2) tolerance which might be due to a down regulation of beta-adrenoceptors and/or to an increase in inhibitory G-proteins.
正性肌力作用可通过增加细胞内钙浓度来实现，钙与收缩蛋白相互作用，和/或通过增加收缩蛋白对钙的敏感性来实现。细胞内钙浓度的增加可由增加环磷酸腺苷（cAMP）的药物产生。细胞内环磷酸腺苷水平的增加可源于腺苷酸环化酶的刺激，这导致环磷酸腺苷生成增加，或源于通过抑制磷酸二酯酶来抑制环磷酸腺苷的降解。环磷酸腺苷的主要作用是在动作电位期间增加钙内向电流，并增强细胞内钙储存对钙的摄取。这导致钙释放增加，从而导致收缩蛋白附近的钙浓度增加。磷酸二酯酶（PDE）抑制剂不依赖于受体，也会产生血管舒张作用（“兼具血管舒张作用的正性肌力药”）。然而，必须牢记磷酸二酯酶的两个潜在缺点：1）正性变时作用和诱发快速性心律失常；2）耐受性，这可能是由于β-肾上腺素能受体下调和/或抑制性G蛋白增加所致。
