Nossaman Bobby, Pankey Edward, Kadowitz Philip
Critical Care Medicine Section, Department of Anesthesiology, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121, USA.
Crit Care Res Pract. 2012;2012:290805. doi: 10.1155/2012/290805. Epub 2012 Feb 28.
The heme-protein soluble guanylyl cyclase (sGC) is the intracellular receptor for nitric oxide (NO). sGC is a heterodimeric enzyme with α and β subunits and contains a heme moiety essential for binding of NO and activation of the enzyme. Stimulation of sGC mediates physiologic responses including smooth muscle relaxation, inhibition of inflammation, and thrombosis. In pathophysiologic states, NO formation and bioavailability can be impaired by oxidative stress and that tolerance to NO donors develops with continuous use. Two classes of compounds have been developed that can directly activate sGC and increase cGMP formation in pathophysiologic conditions when NO formation and bioavailability are impaired or when NO tolerance has developed. In this report, we review current information on the pharmacology of heme-dependent stimulators and heme-independent activators of sGC in animal and in early clinical studies and the potential role these compounds may have in the management of cardiovascular disease.
血红素蛋白可溶性鸟苷酸环化酶（sGC）是一氧化氮（NO）的细胞内受体。sGC是一种由α和β亚基组成的异二聚体酶，含有一个对NO结合和酶激活至关重要的血红素部分。sGC的刺激介导生理反应，包括平滑肌舒张、炎症抑制和血栓形成。在病理生理状态下，氧化应激可损害NO的形成和生物利用度，并且持续使用会导致对NO供体产生耐受性。已经开发出两类化合物，在NO形成和生物利用度受损或出现NO耐受性的病理生理条件下，它们可以直接激活sGC并增加环磷酸鸟苷（cGMP）的形成。在本报告中，我们综述了动物和早期临床研究中关于sGC的血红素依赖性刺激剂和血红素非依赖性激活剂的药理学的当前信息，以及这些化合物在心血管疾病管理中可能发挥的潜在作用。
