Enhanced angiogenesis and relaxation of bladder as early response to bladder outlet obstruction

Int J Urol. 2013 Jan;20(1):116-22. doi: 10.1111/j.1442-2042.2012.03217.x. Epub 2012 Nov 6.

Abstract

Objectives: To provide insights into the pathogenesis of bladder insult secondary to bladder outlet obstruction.

Methods: Six-week-old female Sprague-Dawley rats (n = 80) were divided into eight groups, 10 rats each, according to the duration of bladder outlet obstruction, including 0, 3, 6, 12, 24, 48, 72 h and 1 week. Cystometric parameters were evaluated at 72 h and 1 week after bladder outlet obstruction. Bladder tissues were harvested and Masson's trichrome staining was carried out. Each slide was inspected microscopically and the mean percent collagen area was examined. Changes of collagen deposition and pathological expression of several factors including hypoxia inducible factor-1α, vascular endothelial growth factor, transforming growth factor-β1 and nitric oxide synthase messenger ribonucleic acid of bladders were evaluated.

Results: A significant time-dependent increase in the bladder weight after 6 h and the percent of collagen area after 24 h of bladder outlet obstruction were found. Increase in hypoxia inducible factor-1α, transforming growth factor-β1, inducible nitric oxide synthase messenger ribonucleic acid expression, time-dependent increase in vascular endothelial growth factor, neuronal nitric oxide synthase and endothelial nitric oxide synthase messenger ribonucleic acid expression after 6 h of bladder outlet obstruction was found. The intercontraction interval decreased significantly after 72 h of bladder outlet obstruction.

Conclusions: Cellular remodeling in the bladder secondary to bladder outlet obstruction starts in the early hours and it includes enhanced angiogenesis and bladder relaxation. Early relief from bladder outlet obstruction is helpful to preserve bladder structure and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen / metabolism*
  • Female
  • Hypertrophy
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Muscle Relaxation*
  • Neovascularization, Pathologic*
  • Nitric Oxide Synthase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / metabolism
  • Urinary Bladder / pathology*
  • Urinary Bladder Neck Obstruction / enzymology
  • Urinary Bladder Neck Obstruction / physiopathology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Collagen
  • Nitric Oxide Synthase