Effects of the Peptide Leukotriene Receptor Antagonist ICI 198,615 on the In Vivo and In Vitro Changes in Guinea Pig Bladder Function Which Occur After Sensitization with Ovalbumin

Abstract

Purpose The present studies were designed to determine the effects of in vivo and in vitro administration of ICI 198,615 (ICI), a leukotriene receptor antagonist, on the inflammatory changes that occur in the bladder after sensitization with ovalbumin. Materials and Methods The effect of intravenous administration of ICI on urodynamic changes after instillation of ovalbumin to sensitized guinea pigs was evaluated by in vivo cystometry. Responses of in vitro bladder muscle strips to contractile stimuli and ovalbumin were also evaluated in the presence of ICI. Results In sensitized guinea pigs, in vivo cystometry with ovalbumin induced a marked decrease in bladder capacity and increase in intravesical pressure. Pretreatment with ICI prior to cystometry prevented the ovalbumin-induced changes in capacity and intravesical pressure. There were no significant differences between control and sensitized animals in the responses of in vitro bladder muscle strips to field stimulation or bethanechol. However, maximal contractile responses to ovalbumin were significantly greater in the strips from sensitized animals than in controls. Preincubation with ICI, indomethacin, or pyrilamine alone was unable to inhibit the contractile responses to ovalbumin. However, combined administration of ICI, indomethacin and pyrilamine completely blocked the responses. Conclusions In vivo administration of the leukotriene receptor antagonist ICI 198,615 reversed the urodynamic changes induced by ovalbumin challenge in sensitized guinea pigs. These results indicate that leukotrienes are primarily responsible for the changes in in vivo bladder function associated with sensitization.