Nerve-mediated bladder contraction is impaired by cytokines: involvement of inducible nitric oxide synthase

We investigated the possible involvement of inducible nitric oxide synthase (iNOS) in the effect of cytokines on neuromuscular function in isolated rat bladder strips. Bladder strips were incubated in cell culture medium for 24 h with or without tumour necrosis factor-alpha (TNF-alpha) + interleukin-1beta. Mechanical activity in response to electrical field stimulation and carbachol was recorded in organ baths. Both the electrical field stimulation- and carbachol-induced contractions were reduced by the incubation. The electrical field stimulation-induced contraction was significantly further impaired after prolonged exposure to TNF-alpha + interleukin-beta. This impairment was restored by dexamethasone, the iNOS inhibitor aminoguanidine and partially by brain-derived neurotrophic factor (BDNF). In contrast, carbachol-induced contractions were not affected by cytokines. iNOS protein expression was detected in cytokine-incubated bladder strips by immunohistochemistry and Western blot analysis. The results demonstrated that TNF-alpha + interleukin-1beta impaired nerve-mediated bladder contractions. Aminoguanidine, and to some extent BDNF, exerted neuroprotective effects. (C) 2003 Elsevier B.V. All rights reserved.