Unique vascular responses adhere to the cardiovascular efficacy of the inodilator levosimendan. In particular, selective venodilation appears to explain its clinical benefit during pulmonary hypertension complicated by heart failure with preserved ejection fraction. Vasodilators increase vessel diameter in various parts of the vascular system to different degrees and thereby influence blood pressure, its distribution, and organ perfusion depending on their mechanisms of action. Levosimendan and its long-lived active metabolite OR-1896 mobilize a set of vasodilatory mechanisms, that is, the opening of the ATP-sensitive K⁺ channels and other K⁺ channels on top of a highly selective inhibition of the phosphodiesterase III enzyme. A vessel-specific combination of the above vasodilator mechanisms—in concert with cardiac effects and cardiovascular reflex regulations—illustrates the pharmacological profile of levosimendan in various cardiovascular disorders. While levosimendan has been known to be an inotrope, its properties as an activator of ATP-sensitive K⁺ channels have gone largely ignored with respect to clinical applications. Here, we provide a summary of what is known about the ATP-sensitive K⁺ channel properties in preclinical studies and now for the first time, its ATP-sensitive K⁺ channel properties in a clinical trial.

中文翻译：

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左西孟旦诱导的静脉扩张是由钾通道的开放介导的

独特的血管反应依附于扩张剂左西孟旦的心血管功效。特别是，选择性静脉扩张似乎可以解释其在肺动脉高压合并射血分数保留的心力衰竭期间的临床益处。血管扩张剂不同程度地增加血管系统各部分的血管直径，从而根据其作用机制影响血压、其分布和器官灌注。左西孟旦及其长寿命活性代谢物 OR-1896 调动了一套血管舒张机制，即打开 ATP 敏感的 K ⁺通道和其他 K ⁺在磷酸二酯酶 III 酶的高度选择性抑制之上的通道。上述血管扩张机制的血管特异性组合——与心脏效应和心血管反射调节相一致——说明了左西孟旦在各种心血管疾病中的药理学特征。虽然已知左西孟旦是一种正性肌力药，但其作为 ATP 敏感 K ⁺通道激活剂的特性在临床应用方面已被很大程度上忽略。在这里，我们总结了临床前研究中对 ATP 敏感 K ⁺通道特性的了解，现在首次在临床试验中提供了其 ATP 敏感 K ⁺通道特性。