NOS2 and endothelial dysfunction: Of note, despite the presence of severe hypotension, a considerable degree of vascular dysfunction may exist, a paradox that is best explained as follows: the substantial stimulation of the sGC/cGMP signaling cascade with high formation rates of •NO from iNOS (as shown here by EPR-based measurement of nitrosyl-iron-Hb) may result in a desensitization of this signaling pathway, endothelial dysfunction, and vasoconstriction [28,29].