THE NITRIC-OXIDE SYNTHASE NITRIC-OXIDE AND HEME OXYGENASE CARBON-MONOXIDE PATHWAYS IN THE HUMAN URETER

Objective: To investigate the nitric oxide synthase (NOS)/nitric oxide (NO) and heme oxygenase (HO)/carbon monoxide (GO) pathways in the hum an isolated ureter. Methods: Immunohistochemical studies were performe d. NOS activity was measured by monitoring the converison of [H-3]-arg inine to [H-3]-citrulline. Functional inhibitory effects mediated by N O and CO were assessed, and correlated with cyclic nucleotide levels. Results: The overall innervation of the ureter was moderate, however m ore prominent in the distal segment, Relative to overall innervation, neuronal NOS-immunoreactive (-IR) nerves were few. In the submucosa, n euronal NOS-IR varicose nerves were found closely together with varico se nerves containing calcitonin gene-related peptide immunoreactivity. In the distal ureter, nerve trunks were demonstrated, expressing immu noreactivity for HO-2, Ca2+-dependent NOS activity was 53 +/- 13 pM/mg protein/h, In isolated preparations, NO decreased endothelin-1-induce d contractions in a concentration-dependent manner. In strips exposed to NO, there was a 6-fold increase of the cyclic GMP levels in compari son to control preparations (p < 0.001). CO exerted no effect on induc ed ureteral tone, Conclusions: Neuronal NOS-and HO-2-IR nerves can be demonstrated in the human ureter, where NO, but probably not CO, may c ontribute to the regulation of tone. Although the physiological roles for NO and CO remain to be established, the NOS/NO/cyclic GMP pathway may be a target for drugs producing relaxation of the human ureter, Th e richer innervation of the distal ureter may be of importance for the coordination of ureteral peristalsis and the motility of the ureterov esical junction.