For the treatment of systemic hypertension, pharmacological intervention in nitric oxide-cyclic guanosine monophosphate signaling is a well-explored but unexploited option. In this review, we present the identified drug targets, including oxidases, mitochondria, soluble guanylyl cyclase, phosphodiesterase 1 and 5, and protein kinase G, important compounds that modulate them, and the current status of (pre)clinical development. The mode of action of these compounds is discussed, and based upon this, the clinical opportunities. We conclude that drugs that directly target the enzymes of the nitric oxide-cyclic guanosine monophosphate cascade are currently the most promising compounds, but that none of these compounds is under investigation as a treatment option for systemic hypertension.

中文翻译：

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一氧化氮-cGMP信号在高血压中

对于系统性高血压的治疗，对一氧化氮-环鸟苷单磷酸信号的药物干预是一种经过充分探索但尚未开发的选择。在这篇综述中，我们介绍了已确定的药物靶点，包括氧化酶、线粒体、可溶性鸟苷酸环化酶、磷酸二酯酶 1 和 5 以及蛋白激酶 G、调节它们的重要化合物以及（前）临床开发的现状。讨论了这些化合物的作用方式，并在此基础上讨论了临床机会。我们得出的结论是，直接靶向一氧化氮-环磷酸鸟苷级联酶的药物是目前最有希望的化合物，但这些化合物中没有一种正在研究作为全身性高血压的治疗选择。