It may be speculated that the model of cardiac ischemia represents a pronounced hypoxic environment for the RBCs, leading to formation of NO bioactivity from nitrite with downstream activation of sGC in the RBC, and subsequent extracellular transport of a signal leading to activation of PKG in the cardiac tissue, as shown by the increased cardiac phosphorylation of VASP (32). The gene discussed is PRKG1; the disease is myocardial ischemia.