Fig 1. Two-compartment model of self-cytoprotection against stress as a result of the feedback control interactions among heme-, iron-, porphyrin-, and NO/CO-dependent pathways. The latter interactions are presented in the form of 2 self-regulated feedback loops where coordinated regulation of heme-dependent metabolism can defend against negative stress-induced consequences, among them enhanced cellular oxidant injury, vasospasm, and local inflammation. The left compartment shows how the feedback cycle is capable of suppressing the stress-induced activation of heme oxygenase-1 (HO-1 or HSP32). The right compartment shows how stress-induced activation of the HO-1-CO-cGMP pathway is capable of increasing intracellular cGMP as a protective response against vasospasm, whereas the NO-synthase- NO-cGMP pathway is suppressed by glucocorticosteroid hormones