Figure 4. Proposed cytoprotective mechanisms for nitric oxide.

Nitric oxide (NO) derived from endothelial nitric oxide synthase or from the enzymatic (deoxyhemobin, dexoymyoglobin, cytochromes, xanthine oxidorectase) or nonenyzmatic (acid-dependent disproportionation) reduction of nitrite (NO₂⁻) may protect tissue subjected to ischemia and reperfusion by: a) Inactivation of caspase-3 via the NO-dependent S-nitrosation of the protein; b) cGMP/protein kinase G (cGMP/PKG)-mediated opening of mitochondrial ATP-dependent potassium channels (K_ATP) which reduces the loss of cytochrome C, decreases calcium accumulation within the mitochondria, prevent the opening of the mitochondrial permeablility transition (MPT) pore and decrease apoptosis; c) inhibition of mitochondrial electron transport via the direct or indirect (S-nitrosation) inhibition of Complex I (and possible Complex IV) resulting in decreased reactive oxygen specie (ROS) generation, reduced cytochrome C release and decreased apoptosis.