Bladder contraction, similar to most smooth muscle contraction, is dependent on both the translocation of extracellular calcium across the cell membrane, and the calcium-stimulated release of intracellular bound calcium. Partial outlet obstruction of the urinary bladder induces a marked increase in bladder mass which results in part from a substantial hypertrophy of the smooth muscle elements. In addition, the increase in bladder mass is associated with specific contractile dysfunctions. It is not known if the contractile dysfunction induced by partial outlet obstruction is related to alterations in calcium metabolism. Ryanodine is a pharmacological tool which can be utilized to study the role of intracellular calcium in mediating contractile events. Ryanodine stimulates the loss of intracellular calcium (bound in the sarcoplasmic reticulum) and reduces the participation of intracellular calcium in the contractile response to specific forms of stimulation. The current study investigates the effect of partial outlet obstruction on the ryanodine inhibition of the contractile response of rabbit urinary bladder to field stimulation. New Zealand White rabbits were anesthetized and catheterized with an 8-french Foley catheter. A 00 silk suture was surgically placed around the catheterized urethra, the incision closed, and the catheter removed. After 1, 3, 5 and 7 days of partial outlet obstruction, the bladder was rapidly removed and utilized immediately for contractile studies. The effect of ryanodine (0-80 µM) on the peak response to 2-, 8- and 16-Hz field stimulation at 0.6, 1.8 and 5.4 mM calcium was determined. Ryanodine induced a dose-dependent inhibition of the contractile response of control bladder strips to 2-Hz stimulation (all calcium concentrations), whereas it had no statistically significant inhibitory effect at 8- and 16-Hz stimulation on control tissue. Bladder hypertrophy resulted in a significant and substantial increase in the inhibitory effect of ryanodine at 2, 8 and 16 Hz. In general, the inhibitory effect of ryanodine was most effective at 0.6 mM calcium, and equally effective at 1.8 and 5.4 mM Thus, bladder hypertrophy secondary to partial outlet obstruction induced a marked and significant increase in the inhibitory effect of ryanodine. This indicates that bladder hypertrophy induces a significant alteration in intracellular calcium storage and utilization.
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Levin et al. (2008) studied this question.