van Meel J C, Zimmermann R, Diederen W, Erdman E, Mrwa U
Department of Cardiovascular Pharmacology, Dr Karl Thomae GmbH, Biberach/Riss, Federal Republic of Germany.
Biochem Pharmacol. 1988 Jan 15;37(2):213-20. doi: 10.1016/0006-2952(88)90720-4.
The aim of this study was to investigate whether increasing calcium sensitivity of myofibrils plays a role in the positive inotropic activity of the cardiotonic agent sulmazole. We studied the effects of the stereoisomers of sulmazole on cardiac contractility in vivo and in vitro, arterial blood pressure, cardiac (Na-K)ATPase activity, cAMP/cGMP-phosphodiesterase activity of cardiac and smooth muscle tissue and calcium sensitivity of skinned myocardial fibres. Both stereoisomers of sulmazole were equipotent vasodilators in vivo and this can be explained by their equipotent cAMP- and cGMP-phosphodiesterase inhibitory activities in smooth muscle tissue. However, (+)sulmazole was a much stronger positive inotropic agent than (-)sulmazole in vivo and in vitro. This difference in inotropic activity cannot be explained by cAMP- or cGMP-phosphodiesterase inhibition or (Na-K)ATPase inhibition in cardiac tissue. Only (+)sulmazole produced a dose-dependent increase in calcium sensitivity of skinned myocardial fibres. Therefore, the calcium sensitizing effect on myofibrils evoked by (+)sulmazole might be responsible for the difference in inotropic activity observed between the stereoisomers of sulmazole.
本研究的目的是调查肌原纤维钙敏感性增加是否在强心剂舒马唑的正性肌力活性中发挥作用。我们研究了舒马唑立体异构体对体内和体外心脏收缩力、动脉血压、心脏（钠 - 钾）ATP酶活性、心脏和平滑肌组织的环磷酸腺苷/环磷酸鸟苷磷酸二酯酶活性以及脱膜心肌纤维钙敏感性的影响。舒马唑的两种立体异构体在体内均为等效的血管扩张剂，这可以通过它们在平滑肌组织中对环磷酸腺苷和环磷酸鸟苷磷酸二酯酶的等效抑制活性来解释。然而，在体内和体外，（+）舒马唑都是比（ - ）舒马唑更强的正性肌力剂。这种正性肌力活性的差异不能通过心脏组织中环磷酸腺苷或环磷酸鸟苷磷酸二酯酶抑制或（钠 - 钾）ATP酶抑制来解释。只有（+）舒马唑使脱膜心肌纤维的钙敏感性产生剂量依赖性增加。因此，（+）舒马唑引起的对肌原纤维的钙敏化作用可能是舒马唑立体异构体之间观察到的正性肌力活性差异的原因。
