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 (US)
Pages (from-to)271-276
Number of pages6
JournalJournal of Pediatric Urology
Volume2
Issue number4
DOIs
StatePublished - Aug 1 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, 01.08.2006, 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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AU - Akbal, Cem

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AU - Kaefer, Martin

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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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