Characterization of ureteral dysfunction in an experimental model of congenital bladder outlet obstruction

William F. Santis, Maryrose P. Sullivan, Rita Gobet, Lars J. Cisek, Raymond J. McGoldrick, Subbarao V. Yalla, Craig A Peters

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose: Ureteral dysfunction is a significant sequela of congenital bladder outlet obstruction. However, the structural and functional alterations associated with ureteral dysfunction are not well defined. A model of fetal bladder obstruction in sheep was used to characterize the changes in ureteral smooth muscle, extracellular matrix (ECM) and functional properties in response to bladder outlet obstruction. Materials and Methods: Partial bladder outlet obstruction was created in fetal sheep at gestational age 95 days via placement of a metal ring around the proximal urethra as well as ligation of the urachus. Ureters were harvested at 109 and 135 days (full term = 140 days) to determine the relative composition of smooth muscle, ECM and urothelium by morphometric analysis and to measure DNA and protein concentrations. Ureteral tissue from 135 day gestation obstructed and control sheep was harvested and immediately placed in Krebs solution. Smooth muscle strips (2-3 mm. x 7-8 mm.) were suspended in organ baths. The frequency and amplitude of spontaneous ureteral contractions was as well as the response to electric field stimulation (EFS) were determined. Results: Bladder outlet obstruction caused a significant increase in ureteral weight, smooth muscle mass and total ECM at both 109 and 135 days gestation. Total ureteral DNA was greater in obstructed compared with sham ureters at 135 days gestation. Obstructed ureters demonstrated greater amplitude and frequency of spontaneous contractions as well as more pronounced response to EFS when compared to sham ureters. Conclusions: The fetal ureter responds to bladder obstruction with smooth muscle hyperplasia and hypertrophy which is associated with increased spontaneous activity and augmented response to EFS. ECM content is markedly increased indicating a shift in the balance of connective tissue synthesis and degradation. Congenital post-obstructive ureteral dysfunction therefore appears to be the result of dysregulated smooth muscle cell growth and altered ECM homeostasis producing abnormal ureteral contractility.

Original languageEnglish (US)
Pages (from-to)980-984
Number of pages5
JournalJournal of Urology
Volume163
Issue number3
DOIs
StatePublished - Jan 1 2000

Fingerprint

Urinary Bladder Neck Obstruction
Ureter
Extracellular Matrix
Smooth Muscle
Theoretical Models
Electric Stimulation
Sheep
Pregnancy
Urinary Bladder
Urachus
Urothelium
DNA
Urethra
Baths
Connective Tissue
Hypertrophy
Gestational Age
Smooth Muscle Myocytes
Hyperplasia
Ligation

Keywords

  • Congenital bladder obstruction
  • Extracellular matrix
  • Smooth muscle
  • Ureter

ASJC Scopus subject areas

  • Urology

Cite this

Characterization of ureteral dysfunction in an experimental model of congenital bladder outlet obstruction. / Santis, William F.; Sullivan, Maryrose P.; Gobet, Rita; Cisek, Lars J.; McGoldrick, Raymond J.; Yalla, Subbarao V.; Peters, Craig A.

In: Journal of Urology, Vol. 163, No. 3, 01.01.2000, p. 980-984.

Research output: Contribution to journalArticle

Santis, William F. ; Sullivan, Maryrose P. ; Gobet, Rita ; Cisek, Lars J. ; McGoldrick, Raymond J. ; Yalla, Subbarao V. ; Peters, Craig A. / Characterization of ureteral dysfunction in an experimental model of congenital bladder outlet obstruction. In: Journal of Urology. 2000 ; Vol. 163, No. 3. pp. 980-984.
@article{9ecd078b0bda46b0a9b1a2c6762678b9,
title = "Characterization of ureteral dysfunction in an experimental model of congenital bladder outlet obstruction",
abstract = "Purpose: Ureteral dysfunction is a significant sequela of congenital bladder outlet obstruction. However, the structural and functional alterations associated with ureteral dysfunction are not well defined. A model of fetal bladder obstruction in sheep was used to characterize the changes in ureteral smooth muscle, extracellular matrix (ECM) and functional properties in response to bladder outlet obstruction. Materials and Methods: Partial bladder outlet obstruction was created in fetal sheep at gestational age 95 days via placement of a metal ring around the proximal urethra as well as ligation of the urachus. Ureters were harvested at 109 and 135 days (full term = 140 days) to determine the relative composition of smooth muscle, ECM and urothelium by morphometric analysis and to measure DNA and protein concentrations. Ureteral tissue from 135 day gestation obstructed and control sheep was harvested and immediately placed in Krebs solution. Smooth muscle strips (2-3 mm. x 7-8 mm.) were suspended in organ baths. The frequency and amplitude of spontaneous ureteral contractions was as well as the response to electric field stimulation (EFS) were determined. Results: Bladder outlet obstruction caused a significant increase in ureteral weight, smooth muscle mass and total ECM at both 109 and 135 days gestation. Total ureteral DNA was greater in obstructed compared with sham ureters at 135 days gestation. Obstructed ureters demonstrated greater amplitude and frequency of spontaneous contractions as well as more pronounced response to EFS when compared to sham ureters. Conclusions: The fetal ureter responds to bladder obstruction with smooth muscle hyperplasia and hypertrophy which is associated with increased spontaneous activity and augmented response to EFS. ECM content is markedly increased indicating a shift in the balance of connective tissue synthesis and degradation. Congenital post-obstructive ureteral dysfunction therefore appears to be the result of dysregulated smooth muscle cell growth and altered ECM homeostasis producing abnormal ureteral contractility.",
keywords = "Congenital bladder obstruction, Extracellular matrix, Smooth muscle, Ureter",
author = "Santis, {William F.} and Sullivan, {Maryrose P.} and Rita Gobet and Cisek, {Lars J.} and McGoldrick, {Raymond J.} and Yalla, {Subbarao V.} and Peters, {Craig A}",
year = "2000",
month = "1",
day = "1",
doi = "10.1016/S0022-5347(05)67868-8",
language = "English (US)",
volume = "163",
pages = "980--984",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Characterization of ureteral dysfunction in an experimental model of congenital bladder outlet obstruction

AU - Santis, William F.

AU - Sullivan, Maryrose P.

AU - Gobet, Rita

AU - Cisek, Lars J.

AU - McGoldrick, Raymond J.

AU - Yalla, Subbarao V.

AU - Peters, Craig A

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Purpose: Ureteral dysfunction is a significant sequela of congenital bladder outlet obstruction. However, the structural and functional alterations associated with ureteral dysfunction are not well defined. A model of fetal bladder obstruction in sheep was used to characterize the changes in ureteral smooth muscle, extracellular matrix (ECM) and functional properties in response to bladder outlet obstruction. Materials and Methods: Partial bladder outlet obstruction was created in fetal sheep at gestational age 95 days via placement of a metal ring around the proximal urethra as well as ligation of the urachus. Ureters were harvested at 109 and 135 days (full term = 140 days) to determine the relative composition of smooth muscle, ECM and urothelium by morphometric analysis and to measure DNA and protein concentrations. Ureteral tissue from 135 day gestation obstructed and control sheep was harvested and immediately placed in Krebs solution. Smooth muscle strips (2-3 mm. x 7-8 mm.) were suspended in organ baths. The frequency and amplitude of spontaneous ureteral contractions was as well as the response to electric field stimulation (EFS) were determined. Results: Bladder outlet obstruction caused a significant increase in ureteral weight, smooth muscle mass and total ECM at both 109 and 135 days gestation. Total ureteral DNA was greater in obstructed compared with sham ureters at 135 days gestation. Obstructed ureters demonstrated greater amplitude and frequency of spontaneous contractions as well as more pronounced response to EFS when compared to sham ureters. Conclusions: The fetal ureter responds to bladder obstruction with smooth muscle hyperplasia and hypertrophy which is associated with increased spontaneous activity and augmented response to EFS. ECM content is markedly increased indicating a shift in the balance of connective tissue synthesis and degradation. Congenital post-obstructive ureteral dysfunction therefore appears to be the result of dysregulated smooth muscle cell growth and altered ECM homeostasis producing abnormal ureteral contractility.

AB - Purpose: Ureteral dysfunction is a significant sequela of congenital bladder outlet obstruction. However, the structural and functional alterations associated with ureteral dysfunction are not well defined. A model of fetal bladder obstruction in sheep was used to characterize the changes in ureteral smooth muscle, extracellular matrix (ECM) and functional properties in response to bladder outlet obstruction. Materials and Methods: Partial bladder outlet obstruction was created in fetal sheep at gestational age 95 days via placement of a metal ring around the proximal urethra as well as ligation of the urachus. Ureters were harvested at 109 and 135 days (full term = 140 days) to determine the relative composition of smooth muscle, ECM and urothelium by morphometric analysis and to measure DNA and protein concentrations. Ureteral tissue from 135 day gestation obstructed and control sheep was harvested and immediately placed in Krebs solution. Smooth muscle strips (2-3 mm. x 7-8 mm.) were suspended in organ baths. The frequency and amplitude of spontaneous ureteral contractions was as well as the response to electric field stimulation (EFS) were determined. Results: Bladder outlet obstruction caused a significant increase in ureteral weight, smooth muscle mass and total ECM at both 109 and 135 days gestation. Total ureteral DNA was greater in obstructed compared with sham ureters at 135 days gestation. Obstructed ureters demonstrated greater amplitude and frequency of spontaneous contractions as well as more pronounced response to EFS when compared to sham ureters. Conclusions: The fetal ureter responds to bladder obstruction with smooth muscle hyperplasia and hypertrophy which is associated with increased spontaneous activity and augmented response to EFS. ECM content is markedly increased indicating a shift in the balance of connective tissue synthesis and degradation. Congenital post-obstructive ureteral dysfunction therefore appears to be the result of dysregulated smooth muscle cell growth and altered ECM homeostasis producing abnormal ureteral contractility.

KW - Congenital bladder obstruction

KW - Extracellular matrix

KW - Smooth muscle

KW - Ureter

UR - http://www.scopus.com/inward/record.url?scp=0033954035&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033954035&partnerID=8YFLogxK

U2 - 10.1016/S0022-5347(05)67868-8

DO - 10.1016/S0022-5347(05)67868-8

M3 - Article

C2 - 10688035

AN - SCOPUS:0033954035

VL - 163

SP - 980

EP - 984

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 3

ER -