Protective Role of Nitric Oxide in Kidney and Heart Transplantation

Nitric oxide (NO) is the first identified member of the gasotransmitter family. It is synthesized by a group of enzymes called nitric oxide synthases (NOS). Three structurally distinct isoforms of NOS have been recognized in mammalian cells, namely neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The NO produced by NOS acts on several target proteins and enzymes to ensure vascular homeostasis and other physiological functions. nNOS and eNOS are constitutively expressed while iNOS is a pathological isoform of NOS that contributes to pathophysiology of inflammatory conditions including graft rejection in organ transplantation. Thus, NOS appears to have biphasic actions in biological systems, playing beneficial and detrimental roles. In the setting of organ transplantation, NO produced by constitutive NOS is associated with graft protection while iNOS-derived NO plays a significant detrimental role. In this chapter, the author presents endogenous production of NO as well as its exogenous sources, and then discusses protective effects of constitutive NOS-derived NO in kidney and heart allotransplantation from experimental and clinical perspectives. He also highlights a few isolated studies of graft protection by NO-producing iNOS.