EFFECTS OF THE PEPTIDE LEUKOTRIENE RECEPTOR ANTAGONIST ICI-198,615 ONTHE IN-VIVO AND IN-VITRO CHANGES IN GUINEA-PIG BLADDER FUNCTION WHICHOCCUR AFTER SENSITIZATION WITH OVALBUMIN

Purpose: The present studies were designed to determine the effects of in vivo and in vitro administration of ICI 198,615 (ICI), a leukotrie ne 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 aft er instillation of ovalbumin to sensitized guinea pigs was evaluated b y in vivo cystometry. Responses of in vitro bladder muscle strips to c ontractile stimuli and ovalbumin were also evaluated in the presence o f ICI.Results: In sensitized guinea pigs, in vivo cystometry with oval bumin induced a marked decrease in bladder capacity and increase in in travesical pressure. Pretreatment with ICI prior to cystometry prevent ed 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 s timulation or bethanechol. However, maximal contractile responses to o valbumin were significantly greater in the strips from sensitized anim als than in controls. Preincubation with ICI, indomethacin, or pyrilam ine 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 urody namic changes induced by ovalbumin challenge in sensitized guinea pigs . These results indicate that leukotrienes are primarily responsible f or the changes in in vivo bladder function associated with sensitizati on.