CO-localization of carbon monoxide and nitric oxide synthesizing enzymes in the human urethral, sphincter

Purpose: Ineffective relaxation of the urethral sphincter during micturitio n can result in obstructive voiding symptoms. Several studies suggest carbo n monoxide (CO) acts alongside nitric oxide (NO) as an inhibitory neurotran smitter, and may regulate NO production. We have investigated the distribut ion of the constitutive CO producing enzyme, heme oxygenase-2 (HO-2) and th e NO producing enzyme, neuronal nitric oxide synthase (nNOS), in the human urethra. Materials and Methods: Transverse cryostat sections (12 mu m.) were cut fro m three male membranous and six female urethrae. Double immunofluorescence was-carried out for colocalization of HO-2 with nNOS using standard methodo logy. Results: Nerve trunks showing both HO-2 and nNOS immunoreactivities were id entified in the urethrae in both sexes. In the female urethrae, of 152 gang lionic cell bodies expressing HO-2 or nNOS immunoreactivity, 74.3% exhibite d both HO-2 and nNOS immunoreactivities, 25% exhibited only HO-2 immunoreac tivity and 0.7% exhibited only nNOS immunoreactivity. Conclusions: Immunoreactivity for HO-2 has been demonstrated in neuronal st ructures innervating the male and female urethral sphincters. The dual expr ession of HO-2 with nNOS immunoreactivity in cell bodies and nerves suggest s that there is an interaction between the CO and NO generating systems. Ab normality in these systems may play a role in urethral dysfunction.