FIG. 3.

Role of RBCs in systemic NO metabolism. NO is a vasodilator produced by eNOS enzymes in ECs and mediates vasodilation by activating the soluble guanylate cylase in VSMCs. NO is inactivated by RBCs by reaction with oxyHb forming metHb and nitrate. In the plasma, tissues and RBCs, NO can be oxidized to NO₂⁻ or NO₃⁻ and to other metabolites. Under hypoxic conditions, NO₂⁻ can react with deoxyHb to form NO, which was proposed to mediate hypoxic vasodilation and to inhibit platelet aggregation. Additionally, hypoxic ATP release by RBCs was also proposed to induce vasodilation by activating eNOS in the endothelium. ATP, adenosine triphosphate; ECs, endothelial cells; eNOS, endothelial nitric oxide synthase; sGC, soluble guanylate cyclase; VSMC, vascular smooth muscle cell. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars