CO-LOCALIZATION OF CARBON MONOXIDE AND NITRIC OXIDE SYNTHESIZING ENZYMES IN THE HUMAN URETHRAL SPHINCTER

Abstract

Purpose Ineffective relaxation of the urethral sphincter during micturition can result in obstructive voiding symptoms. Several studies suggest carbon monoxide (CO) acts alongside nitric oxide (NO) as an inhibitory neurotransmitter, and may regulate NO production. We have investigated the distribution of the constitutive CO producing enzyme, heme oxygenase-2 (HO-2) and the NO producing enzyme, neuronal nitric oxide synthase (nNOS), in the human urethra. Materials and Methods Transverse cryostat sections (12 micro m.) were cut from three male membranous and six female urethrae. Double immunofluorescence was carried out for colocalization of HO-2 with nNOS using standard methodology. Results Nerve trunks showing both HO-2 and nNOS immunoreactivities were identified in the urethrae in both sexes. In the female urethrae, of 152 ganglionic cell bodies expressing HO-2 or nNOS immunoreactivity, 74.3% exhibited both HO-2 and nNOS immunoreactivities, 25% exhibited only HO-2 immunoreactivity and 0.7% exhibited only nNOS immunoreactivity. Conclusions Immunoreactivity for HO-2 has been demonstrated in neuronal structures innervating the male and female urethral sphincters. The dual expression of HO-2 with nNOS immunoreactivity in cell bodies and nerves suggests that there is an interaction between the CO and NO generating systems. Abnormality in these systems may play a role in urethral dysfunction.