A team led by scientists at VIB and Ghent University have now shown that, rather than contributing to damage in septic shock, NO may instead be beneficial. When mice with septic shock induced by a lethal TNF challenge were treated with nitrite – which can serve as a source of NO – hypothermia, mitochondrial damage, oxidative stress and dysfunction, tissue infarction and mortality were all attenuated. Nitrite also provided protection against toxicity induced by Gram-negative lipopolysaccharide, although higher doses were needed. Until recently, nitrite was believed to be an inert metabolite of NO but is now considered to be a central homeostatic molecule in NO biology and to serve as an important signalling molecule and regulator of gene expression in its own right. The protection afforded by nitrite treatment was largely abolished in mice lacking the soluble guanylate cyclase 1 subunit, an important intracellular NO receptor and signal transducer. Although the mechanisms underlying the protective effects of nitrite in septic shock are not yet fully understood, the study provides new information about the role of NO in septic shock and suggests new opportunities for treatment.
The study is published in the Journal of Experimental Medicine.