The decompensated detrusor I: the effects of bladder outlet obstruction on the use of intracellular calcium stores.
OBJECTIVE
As in other smooth muscle groups, extracellular calcium influx as well as the release of calcium from intracellular storage sites or sarcoplasmic reticulum occur in response to receptor stimulation. The relative participation of extracellular influx versus intracellular release has recently been shown to be influenced by developmental stage and obstruction. Partial bladder outlet obstruction results in marked hypertrophy of the bladder and produces alterations in contractile function. To understand better how this contractile dysfunction after outlet obstruction is influenced by intracellular calcium handling we tested the effects of 2 drugs with known effects on the sarcoplasmic reticulum.


METHODS
We evaluated ryanodine, which blocks the release of calcium from the sarcoplasmic reticulum, and thapsigargin, which blocks the ability of the sarcoplasmic reticulum to pump cytosolic calcium back into the storage sites. Rabbit bladders were obstructed for different periods, after which detrusor muscle strips were harvested and contractile performance was evaluated in the absence and presence of ryanodine and thapsigargin.


RESULTS
In the early phases of outlet obstruction the release of intracellular calcium increased significantly. With prolonged obstruction and detrusor decompensation the intracellular storage sites lost the ability to contribute to the generation 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 infravesical obstruction.
Rohrmann
D
D
Department of Urology, Children's Hospital of Philadelphia, Pennsylvania, USA.
Levin
R M
RM
Duckett
J W
JW
Zderic
S A
SA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000503:physiopathology*; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism* / Q000503:physiopathology
D002121:Calcium Channel Blockers; D013729:Terpenes; D012433:Ryanodine; D019284:Thapsigargin; D002118:Calcium