Nossaman Bobby D, Kadowitz Philip J
Department of Anesthesiology, Section of Critical Care Medicine, Ochsner Clinic Foundation, and ; The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA ; Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA.
Ochsner J. 2013 Spring;13(1):147-56.
Soluble guanylyl cyclase (sGC) is expressed in mammalian cytoplasm and catalyzes the synthesis of the second messenger guanosine 3',5'-monophosphate (cGMP) involved in important physiological functions such as relaxation of vascular smooth muscle, inhibition of platelet aggregation, modulation of inflammation, and control of vascular permeability. sGC is the intracellular receptor for nitric oxide (NO) and the active moiety in traditional organic nitrate therapy, recently as an inhalant in the intensive care unit and experimentally in improving microcirculatory flow in shock. However, dysfunction of the heme moiety on sGC occurs in a number of cardiovascular diseases, which reduces NO effectiveness.
In this review, we examine animal studies and early clinical trials on agents that can directly stimulate sGC and may have future clinical application in cardiovascular disease and in perioperative care.
Animal and early clinical studies have shown that sGC stimulator agents have great promise for treating cardiopulmonary disorders and may also have a role in modulating the inflammatory response observed in perioperative care.
可溶性鸟苷酸环化酶（sGC）在哺乳动物细胞质中表达，催化第二信使3',5'-环磷酸鸟苷（cGMP）的合成，cGMP参与重要的生理功能，如血管平滑肌舒张、抑制血小板聚集、调节炎症以及控制血管通透性。sGC是一氧化氮（NO）的细胞内受体，也是传统有机硝酸盐疗法中的活性部分，最近在重症监护病房作为吸入剂使用，并在实验中用于改善休克时的微循环血流。然而，sGC上的血红素部分功能障碍在多种心血管疾病中出现，这降低了NO的有效性。
在本综述中，我们研究了关于可直接刺激sGC且可能在心血管疾病和围手术期护理中具有未来临床应用的药物的动物研究和早期临床试验。
动物和早期临床研究表明，sGC刺激剂在治疗心肺疾病方面具有巨大潜力，并且在调节围手术期护理中观察到的炎症反应方面可能也发挥作用。
