Intravesical pressure induces hyperplasia and hypertrophy of human bladder smooth muscle cells mediated by muscarinic receptors.
PURPOSE
Bladder outlet obstruction with intravesical pressures exceeding 40 cmH(2)O results in a progressive increase in wall thickness, eventually causing low compliance. We investigated whether intravesical pressure induces hypertrophy and/or hyperplasia of human bladder smooth muscle cells (HBSMC) mediated by a muscarinic (M) receptor, and evaluated the relationship between intravesical pressure and M receptor antagonists.


MATERIALS AND METHODS
HBSMC were exposed to 40 cmH(2)O pressure and/or acetylcholine (10 nM-100 microM) for 24h. Cells exposed to hydrostatic pressure were treated with either 1 microM AF-DX 16 (M(2) antagonist), 1 microM 4-DAMP (M(3) antagonist) or 1 microM atropine (both M(2) and M(3) antagonists). DNA and protein synthesis of HBSMC were measured by (3)H-thymidine and leucine incorporation assays, respectively.


RESULTS
(3)H-thymidine incorporation increased following exposure to increasing concentrations of acetylcholine (at 100 microM, P<0.05). When cells were exposed to 40 cmH(2)O for 24h, (3)H-thymidine incorporation increased by 31.4%, 33.3% and 39.5% in 1 microM, 10 microM and 100 microM of acetylcholine, respectively. With exposure to 100 microM acetylcholine, a hydrostatic pressure of 40 cm, and both of these together, (3)H-thymidine incorporation increased by 16.7%, 25.9% and 39.4%, respectively, and leucine incorporation increased by 66.5%, 66.5% and 81.8%, respectively (P<0.05). Antimuscarinic agents had no apparent effect on the proliferative rate of cells grown at atmospheric pressure, but there was a dramatic decrease in thymidine and leucine incorporation for cells that were simultaneously exposed to increased hydrostatic pressure, most pronounced when the combined M(2)/M(3) receptor antagonist was applied.


CONCLUSIONS
Intravesical pressure may induce hypertrophy/hyperplasia of HBSMC mediated by M receptors. Early use of an M receptor antagonist in cases of high intravesical pressure may have a positive effect on bladder compliance.