This may be because of the specific (sub)compartmentalization of eNOS within the vessel wall and its cellular components,35–38 the unique anatomy and function of the vascular tree39 and its relationship with the circulating blood cells,14 and the different half-life and distribution kinetics of the NO metabolites within the blood and the tissues.9,16,24,40–42 The functional differences of the pathway in RBCs or the vasculature may become prominent under specific pathophysiological conditions such as endothelial dysfunction or blood disorders. The gene discussed is NOS3; the disease is endothelial dysfunction.