HEME OXYGENASE-2 - ENDOTHELIAL AND NEURONAL LOCALIZATION AND ROLE IN ENDOTHELIUM-DEPENDENT RELAXATION

Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has b een localized by immunohistochemistry to endothelial cells and adventi tial nerves of blood vessels. HO-2 is also localized to neurons in aut onomic ganglia, including the petrosal, superior cervical, and nodose ganglia, as well as ganglia in the myenteric plexus of the intestine. Enzyme studies demonstrated that tin protoporphyrin-9 is a selective i nhibitor of HO with approximate to 10-fold selectivity for HO over end othelial nitric oxide synthase (NOS) and soluble guanylyl cyclase. Inh ibition of HO activity by tin protoporphyrin 9 reverses the component of endothelial-derived relaxation of porcine distal pulmonary arteries not reversed by an inhibitor of NOS. Thus, CO, like NO, may have endo thelial-derived relaxing activity. The similarity of NOS and HO-2 loca lizations and functions in blood vessels and the autonomic nervous sys tem implies complementary and possibly coordinated physiologic roles f or these two mediators.