THE DECOMPENSATED DETRUSOR I - THE EFFECTS OF BLADDER OUTLET OBSTRUCTION ON THE USE OF INTRACELLULAR CALCIUM STORES

Purpose: As in other smooth muscle groups, extracellular calcium influ x as well as the release of calcium from intracellular storage sites o r sarcoplasmic reticulum-occur in response to receptor stimulation. Th e relative participation of extracellular influx versus intracellular release has recently been shown to be influenced by developmental stag e and obstruction. Partial bladder outlet obstruction results in marke d hypertrophy of the bladder and produces alterations in contractile f unction. To understand better how this contractile dysfunction after o utlet obstruction is influenced by intracellular calcium handling we t ested the effects of 2 drugs with known effects on the sarcoplasmic re ticulum. Materials and Methods: We evaluated ryanodine, which blocks t he release of calcium from the sarcoplasmic reticulum, and thapsigargi n, which blocks the ability of the sarcoplasmic reticulum to pump cyto solic calcium back into the storage sites. Rabbit bladders were obstru cted for different periods, after which detrusor muscle strips were ha rvested and contractile performance was evaluated in the absence and p resence of ryanodine and thapsigargin. Results: In the early phases of outlet obstruction the release of intracellular calcium increased sig nificantly. With prolonged obstruction and detrusor decompensation the intracellular storage sites lost the ability to contribute to the gen eration of contractile force. Conclusions: Alterations in the calcium handling ability of the smooth muscle cell appear to have an important role in the process of decompensation of bladder function in infraves ical obstruction.