S-Nitrosothiols: a class of nitric oxide-donor drugs

Abstract

Nitric oxide (NO) was originally described as the principal endothelium-derived relaxing factor, but it is now known to subserve a variety of functions throughout the body, both physiological and pathophysiological. NO-donor drugs decompose in the body, by a variety of mechanisms, to generate NO. Such drugs have been used for many years in cardiovascular therapeutics, in particular the organic nitrates for the prevention and treatment of angina pectoris and sodium nitroprusside for the treatment of hypertensive emergencies. However, patients taking long-term nitrates often develop tolerance, and prolonged nitroprusside administration can give rise to cyanide accumulation in the body. Newer NO-donor drugs, in particular the S-nitrosothiols, offer advantages over the existing drugs, since they do not share these drawbacks, and initial small clinical studies suggest that they may be of benefit in a variety of cardiovascular disorders. Here we briefly review the chemistry and physiology of NO, and discuss the chemistry and clinical possibilities of the S-nitrosothiols.

Control of Plasma Nitric Oxide Bioactivity by Perfluorocarbons

“…As potent systemic vasodilators and platelet inhibitors, RSNOs have been evaluated in the treatment of various cardiovascular complications, including thrombosis, vasospasm, preeclampsia, and ischemia/reperfusion injury. [12][13][14] Furthermore, because of their bronchodilating properties and the fact that the airway level of RSNOs is reduced in asthma and cystic fibrosis patients, RSNOs are considered as promising therapeutics for pulmonary conditions. 41,42 Finally, RSNOs may be used as antiviral and antimicrobial agents, because they inhibit viral protease enzymes and possess a strong bacteriostatic effect.…”

“…[3][4][5][6][7] Because RSNOs are relatively stable and can release NO when required on reaction with various reducing agents, 8,9 they may serve as a buffering system that magnifies the range of NO action along the vascular tree. 10,11 Although the pharmacological potential of RSNO is well appreciated, [12][13][14] the role of plasma NO and the mechanism of endogenous RSNO formation under physiological conditions are a source of considerable debate. 15 The apparent limitation for plasma NO to exert its biological function is the constant presence of abundant hemoglobin (10 mmol/L) from red blood cells that converts NO into inactive metabolites at near-diffusion-limited rates.…”

Regulation of protein function by S-nitrosation and S-glutathionylation: processes and targets in cardiovascular pathophysiology

“…In contrast to classic NO donors used in pharmacotherapy, S-nitrosothiols could be promising substitutes as they do not induce the development of tolerance or cyanide poisoning (Al-Sa'doni and Ferro, 2000;Belcastro et al, 2017). S-nitrosothiols proved effective in a variety of cardiovascular disorders, including e.g.…”

“…Cellular responses to GSNO have in fact received great attention during the last few years (Broniowska et al, 2013). Indeed, GSNO does not induce any tolerance or oxidative stress (Al-Sa'doni and Ferro, 2000;Belcastro et al, 2017). To date, there have been nearly 20 clinical trials investigating the therapeutic efficacy of GSNO in multiple pathological contexts, and most of them have focused on its effects in cardiovascular diseases (Gaucher et al, 2013).…”

“…As mentioned above, in a therapeutic perspective S-nitrosothiols (GSNO in the first place) may represent promising NO-donor molecules, compared to other NO-related therapeutics limited by tolerance phenomena and oxidant stress (Al-Sa'doni and Ferro, 2000;Hornyák et al, 2011).…”