INHIBITORY INNERVATION OF THE GUINEA-PIG URETHRA - ROLES OF CO, NO AND VIP

The inhibitory innervation of guinea-pig urethral smooth muscle was in vestigated histochemically and functionally. The distribution of immun oreactivities to haem oxygenases (HO), neuronal NO synthase (nNOS), an d vasoactive intestinal polypeptide (VIP) was studied, and the functio nal effects of the corresponding putative transmitters, CO, NO, and VI P, were assessed. HO-2 immunoreactivity was found in all nerve cell bo dies of intramural ganglia, localized between smooth muscle bundles in the detrusor, bladder base and proximal urethra. About 70% of the gan glionic cell bodies were also NOS-immunoreactive (IR), whereas a minor part was VIP-LR. Some ganglion cells exhibiting tyrosine hydroxylase (TH) activity were demonstrated. Rich numbers of NOS-IR varicose nerve terminals could be found innervating the smooth muscle of the urethra , whereas VIP-IR terminals were less numerous. A rich number of TH-IR terminals were observed. The bladder showed a similar distribution of nerves, although only a few number of TH-IR nerves could be found. In bladder preparations exposed to sodium nitroprusside, cGMP-IR cells co uld be seen, forming an interconnecting network with long spindle-shap ed processes. The cGMP-IR cells were especially abundant in the outer smooth muscle layers of the bladder, but less numerous in the urethra. In urethral strip preparations, electrical field stimulation evoked l ong-lasting frequency-dependent relaxations. The relaxations were not inhibited by the NO-synthesis inhibitor, L-NOARG, or enhanced by the N O-precursor, L-arginine. The haem precursor, 5-aminolevulinic acid (5- ALA), or the inhibitor of guanylate cyclase, ODQ, did not affect the u rethral relaxations. Exogenously applied NO, SIN-1, and VIP relaxed th e preparations by approximately 50%, whereas the relaxation evoked by exogenous CO was minor. These results suggest that CO probably is not involved in non-adrenergic, non-cholinergic inhibitory control of the guinea-pig urethra, where a non-NO/cGMP mediated relaxation seems to b e predominant. (C) 1998 Elsevier Science B.V. All rights reserved.