Enhanced production of nitric oxide may contribute to the induction of detrusor underactivity in sucrose fed rats

Objective: In a previous study we showed that sucrose feeding creates cystometric properties resembling detrusor underactivity (DU) associated with enhanced production of nitric oxide (NO) in rats. Our present objective was to evaluate the possible role of P2X-purinergic and cholinergic receptors as molecular mechanisms underlying DU-like conditions associated with enhanced production of NO and altered contractile properties in rat bladder strips. Materials and methods: Female Sprague-Dawley rats had ad-libitum access to 5% sucrose in water for two to four weeks. Isometric detrusor contractions were characterized in response to electrical field stimulation, the cholinergic agonist carbachol, the P2X agonist alpha, beta-methylene-ATP or KCl-induced depolarization. ATP and NO release rates were determined from bladder strips after stimulation of cholinergic or P2X-type purinergic receptors. Results: Electrical field stimulations generated stronger contractile responses in the strips from sucrose fed animals, while KCl induced similar contractions. The release of ATP after cholinergic or purinergic stimulation was similar in control or sucrose fed bladder strips. Nonetheless, NO production was significantly higher when pharmacologically triggered with either cholinergic or purinergic stimulation in the bladder strips from rats drinking sucrose for four weeks. The contractile responses to carbachol or abMe-ATP were also significantly reduced in this group. Conclusions: Detrusor contractions in these underactive-like conditions are gradual, and may be generated by excessive NO production that is mediated by individual activation of cholinergic or purinergic receptors, with higher effects by the latest. Our results suggest that nitric oxide production and not impaired contractile mechanisms are involved in this rat model of detrusor underactivity.