LOCALIZATION OF NITRIC-OXIDE SYNTHASE AND HAEMOXYGENASE, AND FUNCTIONAL-EFFECTS OF NITRIC-OXIDE AND CARBON-MONOXIDE IN THE PIG AND HUMAN INTRAVESICAL URETER

The distribution of nitric oxide synthase (NOS)-immunoreactive (IR) an d haemoxygenase (HO)-IR nerves was investigated in the pig and human i ntravesical ureter (IVU). NOS activity was measured by monitoring the conversion of [H-3]-arginine to [H-3]-citrulline. Effects of NO and re sulting changes in cyclic nucleotide concentrations were assessed in v itro. The effects of carbon monoxide (GO) on IVU motility was also tes ted. Immunohistochemistry revealed an abundant overall innervation of the IVU and numerous NOS-IR nerves. Nerve trunks were also found expre ssing immunoreactivity for HO-1, one of the enzymes synthetising CO. S imilar profiles of nerve structures expressing immunoreactivities for NOS and tyrosine-hydroxylase (TH), as well as NOS and vasoactive intes tinal peptide (VIP) were demonstrated. In the pig IVU, measurement of NOS activity revealed a moderate calcium-dependent catalytic activity. NO and the NO-donor SIN-I reduced in a concentration-dependent manner serotonin-induced contractions of pig and human IVU, and the spontane ous contractions of pig IVU. In pig IVU strips precontracted with the thromboxane analogue U-46619, tetrodotoxin-sensitive relaxations were abolished by the NOS inhibitor N-G-nitro-L-arginine. CO exerted no sig nificant effect on spontaneous or induced contractions in the pig and human IVU. In precontracted strips of the pig and human IVU exposed to SIN-I or NO, significant increases of cyclic GMP levels were measured in comparison to control preparations. The results suggest that the L -arginine/NO/cyclic GMP pathway may play a role in the regulation of t he valve function in the uretero-vesical junction (UVJ). A role for CO in the UVJ has yet to be established. (C) 1997 Wiley-Liss, Inc.