Scholz H
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, FRG.
Basic Res Cardiol. 1989;84 Suppl 1:3-7. doi: 10.1007/BF02650341.
This review deals with the principal mechanisms which are known to play a role in positive inotropism: 1) The myoplasmic Ca2+ concentration may be increased by increases in cyclic AMP. Beside receptor-mediated stimulation (isoprenaline) or direct stimulation (forskolin) of the adenylate cyclase, the cyclic AMP may be increased by phosphodiesterase inhibition; 2) Cyclic AMP-independent activation of Ca2+ channels can be brought about by alpha-adrenergic agents (phenylephrine) or so-called calcium agonists; 3) Only a small increase in myoplasmic Na+ concentration can greatly enhance the force of contraction by an increase in the intracellular Ca2+ concentration. This is possible by inhibition of the Na+/K+-ATPase (glycosides) or by prolongation of the open state of Na+ channels (DPI 201-106); 4) A direct inhibition of the Na+/Ca2+ exchange has been discussed for amiloride; 5) A prolongation of the action potential induced by K+ channel-inhibiting agents such as 4-amino-pyridine may increase the myoplasmic Ca2+ concentration by a prolongation of the slow Ca2+ inward current; 6) An increased Ca2+ sensitivity of the contractile proteins has been demonstrated for a number of compounds in vitro; the contribution of such an effect to the overall positive inotropism is unknown because a calcium sensitizer without any effects on calcium or sodium movements is not yet available.
1）环磷酸腺苷（cAMP）增加可使肌浆内钙离子浓度升高。除了通过受体介导刺激（异丙肾上腺素）或直接刺激（福斯可林）腺苷酸环化酶外，抑制磷酸二酯酶也可使cAMP增加；2）α-肾上腺素能药物（去氧肾上腺素）或所谓的钙激动剂可引起不依赖cAMP的钙通道激活；3）肌浆内钠离子浓度仅小幅升高，即可通过增加细胞内钙离子浓度显著增强收缩力。这可通过抑制钠钾ATP酶（糖苷类）或延长钠通道开放状态（DPI 201-106）实现；4）已讨论过氨氯地平对钠钙交换的直接抑制作用；5）钾通道抑制剂（如4-氨基吡啶）诱导的动作电位延长，可能通过延长缓慢的钙内向电流增加肌浆内钙离子浓度；6）在体外已证实多种化合物可增加收缩蛋白对钙离子的敏感性；由于尚未找到对钙或钠转运无影响的钙敏化剂，这种效应在总体正性肌力作用中的贡献尚不清楚。
