Neuronal-derived nitric oxide modulates the activity of mouse detrusor smooth muscle

Abstract

Aims We investigated the roles of neuronal-derived nitric oxide (NO) in the modulation of spontaneous activity of mouse detrusor smooth muscle. Methods Detrusor smooth muscle strips were isolated from nNOS gene knock-out (nNOS -/-) mice and their wild type siblings (nNOS +/+). The properties of smooth muscle cells were assessed using intracellular electrophysiology and Ca 2+ imaging by laser-scanning confocal microscopy. The effects of an nNOS inhibitor, 7-nitro indazole (7-NI) on electrically evoked contractility were assessed using nNOS +/+ mouse detrusor strips. Results In spontaneously active cells, the frequency of spontaneous action potentials (sAPs) and whole cell Ca 2+ flashes in nNOS -/- preparations was lower than that in the nNOS +/+ preparations. The frequency of sAPs was enhanced by a nitric oxide donor, diethylamine NONOate sodium salt (NONOate; 100μM), both when used alone and when the cGMP pathway was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, 10μM). 7-NI (100μM) significantly suppressed the electrically evoked contraction of mouse detrusor strips. Conclusions We suggest that neuronal-derived NO facilitates the generation of spontaneous activity via a cGMP-independent pathway, and consequently enhances the evoked contraction of detrusor. Dysregulation of nNOS containing nerves may underlie bladder pathologies. Copyright © 2012 Wiley Periodicals, Inc.