Nitrosoglutathione (GSNO) is an S-nitrosylthiol NO donor based on natural glutathione [1]. Nitrosoglutathione is an effective smooth muscle relaxant and platelet aggregation inhibitor, capable of inhibiting the AT1 receptor responses dependent and independent of brain vascular angiotensin II [2]. Nitrosoglutathione selectively inhibits platelet and NF-κB activation [3].
In vitro, Nitrosoglutathione (1-100μM; 5h) can activate Ras, Src and ERK1/2 MAP kinases and promote HeLa cell proliferation. However, when HeLa cells are exposed to 1mM Nitrosoglutathione, cell proliferation is inhibited [4]. Nitrosoglutathione (500μM; 2h) treatment of neutrophils reduces TNFα-induced NF-κB activity and inhibits IκBα degradation [5].
In vivo, Nitrosoglutathione (8mg/kg/day; 7d; i.v.) significantly reduces systolic blood pressure, diastolic blood pressure and mean arterial pressure in rats with preeclampsia (PE) from day 14 to day 20 [6]. Nitrosoglutathione (0.2 and 0.6mg/kg; single administration; i.v.) significantly inhibits the production of superoxide in rats with ischemia/reperfusion injury models and inhibits NF-κB activation, iNOS induction and 3-nitrotyrosine expression, and upregulats the expression of endothelial NOS in flap vessels [7].
References:
[1] Bouressam ML, Lecat S, Raoul A, et al. S-nitrosoglutathione inhibits cerebrovascular angiotensin II-dependent and -independent AT receptor responses: A possible role of S-nitrosation. Br J Pharmacol. 2019;176(12):2049-2062.
[2] Jensen DE, Belka GK, Du Bois GC. S-Nitrosoglutathione is a substrate for rat alcohol dehydrogenase class III isoenzyme. Biochem J. 1998;331 (Pt 2) (Pt 2):659-668.
[3] Fortenberry J D, Owens M L, Brown L A S. S-nitrosoglutathione enhances neutrophil DNA fragmentation and cell death[J]. American Journal of Physiology-Lung Cellular and Molecular Physiology, 1999, 276(3): L435-L442.
[4] Batista W L, Ogata F T, Curcio M F, et al. S-nitrosoglutathione and endothelial nitric oxide synthase-derived nitric oxide regulate compartmentalized ras S-nitrosylation and stimulate cell proliferation[J]. Antioxidants & redox signaling, 2013, 18(3): 221-238.
[5] Fortenberry J D, Owens M L, Chen N X, et al. S-nitrosoglutathione inhibits TNF-α-induced NF κ B activation in neutrophils[J]. Inflammation Research, 2001, 50(2): 89-95.
[6] Brown, Caneta et al. “The effects of S-nitrosoglutathione and S-nitroso-N-acetyl-D, L-penicillamine in a rat model of pre-eclampsia.” Journal of natural science, biology, and medicine vol. 4,2 (2013): 330-5.
[7] Kuo YR, Wang FS, Jeng SF, Lutz BS, Huang HC, Yang KD. Nitrosoglutathione promotes flap survival via suppression of reperfusion injury-induced superoxide and inducible nitric oxide synthase induction. J Trauma. 2004;57(5):1025-1031.