Intravesical pressure induces hyperplasia and hypertrophy of human bladder smooth muscle cells mediated by muscarinic receptors

Sang Don Lee, Cem Akbal, Chaeyong Jung, Martin Kaefer

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose: Bladder outlet obstruction with intravesical pressures exceeding 40 cmH2O 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 cmH2O pressure and/or acetylcholine (10 nM-100 μM) for 24 h. Cells exposed to hydrostatic pressure were treated with either 1 μM AF-DX 16 (M2 antagonist), 1 μM 4-DAMP (M3 antagonist) or 1 μM atropine (both M2 and M3 antagonists). DNA and protein synthesis of HBSMC were measured by 3H-thymidine and leucine incorporation assays, respectively. Results: 3H-thymidine incorporation increased following exposure to increasing concentrations of acetylcholine (at 100 μM, P < 0.05). When cells were exposed to 40 cmH2O for 24 h, 3H-thymidine incorporation increased by 31.4%, 33.3% and 39.5% in 1 μM, 10 μM and 100 μM of acetylcholine, respectively. With exposure to 100 μM acetylcholine, a hydrostatic pressure of 40 cm, and both of these together, 3H-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 M2/M3 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.

Original languageEnglish
Pages (from-to)271-276
Number of pages6
JournalJournal of Pediatric Urology
Volume2
Issue number4
DOIs
StatePublished - Aug 2006

Fingerprint

Muscarinic Receptors
Hypertrophy
Smooth Muscle Myocytes
Hyperplasia
Urinary Bladder
Thymidine
Pressure
Acetylcholine
Hydrostatic Pressure
Leucine
Compliance
Urinary Bladder Neck Obstruction
Muscarinic Antagonists
Atmospheric Pressure
Atropine
DNA
Proteins

Keywords

  • Bladder smooth muscle
  • Hyperplasia
  • Hypertrophy
  • Intravesical pressure
  • Muscarinic receptor

ASJC Scopus subject areas

  • Urology
  • Pediatrics, Perinatology, and Child Health

Cite this

Intravesical pressure induces hyperplasia and hypertrophy of human bladder smooth muscle cells mediated by muscarinic receptors. / Lee, Sang Don; Akbal, Cem; Jung, Chaeyong; Kaefer, Martin.

In: Journal of Pediatric Urology, Vol. 2, No. 4, 08.2006, p. 271-276.

Research output: Contribution to journalArticle

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abstract = "Purpose: Bladder outlet obstruction with intravesical pressures exceeding 40 cmH2O 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 cmH2O pressure and/or acetylcholine (10 nM-100 μM) for 24 h. Cells exposed to hydrostatic pressure were treated with either 1 μM AF-DX 16 (M2 antagonist), 1 μM 4-DAMP (M3 antagonist) or 1 μM atropine (both M2 and M3 antagonists). DNA and protein synthesis of HBSMC were measured by 3H-thymidine and leucine incorporation assays, respectively. Results: 3H-thymidine incorporation increased following exposure to increasing concentrations of acetylcholine (at 100 μM, P < 0.05). When cells were exposed to 40 cmH2O for 24 h, 3H-thymidine incorporation increased by 31.4{\%}, 33.3{\%} and 39.5{\%} in 1 μM, 10 μM and 100 μM of acetylcholine, respectively. With exposure to 100 μM acetylcholine, a hydrostatic pressure of 40 cm, and both of these together, 3H-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 M2/M3 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.",
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N2 - Purpose: Bladder outlet obstruction with intravesical pressures exceeding 40 cmH2O 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 cmH2O pressure and/or acetylcholine (10 nM-100 μM) for 24 h. Cells exposed to hydrostatic pressure were treated with either 1 μM AF-DX 16 (M2 antagonist), 1 μM 4-DAMP (M3 antagonist) or 1 μM atropine (both M2 and M3 antagonists). DNA and protein synthesis of HBSMC were measured by 3H-thymidine and leucine incorporation assays, respectively. Results: 3H-thymidine incorporation increased following exposure to increasing concentrations of acetylcholine (at 100 μM, P < 0.05). When cells were exposed to 40 cmH2O for 24 h, 3H-thymidine incorporation increased by 31.4%, 33.3% and 39.5% in 1 μM, 10 μM and 100 μM of acetylcholine, respectively. With exposure to 100 μM acetylcholine, a hydrostatic pressure of 40 cm, and both of these together, 3H-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 M2/M3 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.

AB - Purpose: Bladder outlet obstruction with intravesical pressures exceeding 40 cmH2O 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 cmH2O pressure and/or acetylcholine (10 nM-100 μM) for 24 h. Cells exposed to hydrostatic pressure were treated with either 1 μM AF-DX 16 (M2 antagonist), 1 μM 4-DAMP (M3 antagonist) or 1 μM atropine (both M2 and M3 antagonists). DNA and protein synthesis of HBSMC were measured by 3H-thymidine and leucine incorporation assays, respectively. Results: 3H-thymidine incorporation increased following exposure to increasing concentrations of acetylcholine (at 100 μM, P < 0.05). When cells were exposed to 40 cmH2O for 24 h, 3H-thymidine incorporation increased by 31.4%, 33.3% and 39.5% in 1 μM, 10 μM and 100 μM of acetylcholine, respectively. With exposure to 100 μM acetylcholine, a hydrostatic pressure of 40 cm, and both of these together, 3H-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 M2/M3 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.

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