Reserpine-induced detrusor hyperreflexia: an in vivo model for studying smooth muscle relaxants at urinary bladder...

A new in vivo model for studying the effects of smooth muscle relaxant drugs at urinary bladder level has been developed. This involves the determination of a cystometrogram at a physiological filling rate in urethane anesthetized rats. The amount of infused saline required to elicit TTX-sensitive rhythmic contractions (micturition reflex) of urinary bladder was choosen as end point to evaluate the effect of test substances. Reserpine pretreatment significantly reduced the volume of saline required to elicit the micturition reflex. The effect of reserpine can be reproduced by intravenous prazosin, but not by propranolol or yohimbine, in control rats. Intravenous, but not topical, hexamethonium reversed the effects of reserpine pretreatment on the amount of infused saline required to elicit rhythmic contractions. The nature of rhythmic contractions produced by saline filling of the urinary bladder in these experimental conditions, as well as the potential mechanism(s) involved in the effects of reserpine, are discussed in view of the existing literature on the physiology and pharmacology of the micturition reflex. The effects of various drugs commonly used to produce a relaxation of bladder muscle suggest that this model might be useful for detecting substances of potential therapeutic usefulness in the treatment of bladder hypermotility disorders.