Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications

Critical Care Medicine Section, Department of Anesthesiology, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121, USA.
Critical care research and practice 02/2012; 2012(23):290805. DOI: 10.1155/2012/290805
Source: PubMed


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.

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    • "As a result, the cell is getting short of bioactive NO and responses with up-regulation of NOS and enzymes engaged in detoxification of ROS, such as catalase and superoxide dismutase6. Combined with ROS and degraded further to reactive nitrogen oxide species (RNOS), NO can damage the cell of its origin and thereby cause a variety of diseases17. However, the role of NO in the course of pancreatitis remains controversial. "
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    • "Previous studies showed that FIR could increase generation of nitric oxide (NO) and calmodulin in cells [19, 20, 36]. Associated physiological roles of NO include immune regulation [37, 38], neurotransmission [39], and vascular smooth muscle relaxation [40, 41]. Previous reports have demonstrated that NO in endothelial cells plays an important role in regulating smooth muscle [42]. "
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