Possible Role of Endothelin-1 in the Rabbit Urinary Bladder Hyperplasia Secondary to Partial Bladder Outlet Obstruction

Masood A. Khan Department of Urology, Royal Free and University College Medical School, University College London, Department of Vascular Surgery, St. Mary's Hospital, London, UK, the Departments of Immunocytochemistry and Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, University College London, London, UK

Nileema Shukla Department of Urology, Royal Free and University College Medical School, University College London, Department of Vascular Surgery, St. Mary's Hospital, London, UK, the Departments of Immunocytochemistry and Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, University College London, London, UK

John Auld Department of Urology, Royal Free and University College Medical School, University College London, Department of Vascular Surgery, St. Mary's Hospital, London, UK, the Departments of Immunocytochemistry and Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, University College London, London, UK

Cecil S. Thompson Department of Urology, Royal Free and University College Medical School, University College London, Department of Vascular Surgery, St. Mary's Hospital, London, UK, the Departments of Immunocytochemistry and Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, University College London, London, UK

Faiz H. Mumtaz Department of Urology, Royal Free and University College Medical School, University College London, Department of Vascular Surgery, St. Mary's Hospital, London, UK, the Departments of Immunocytochemistry and Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, University College London, London, UK

Gerard P. Stansby Department of Urology, Royal Free and University College Medical School, University College London, Department of Vascular Surgery, St. Mary's Hospital, London, UK, the Departments of Immunocytochemistry and Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, University College London, London, UK

Robert J. Morgan Department of Urology, Royal Free and University College Medical School, University College London, Department of Vascular Surgery, St. Mary's Hospital, London, UK, the Departments of Immunocytochemistry and Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, University College London, London, UK

Dimitri P. Mikhailidis Department of Urology, Royal Free and University College Medical School, University College London, Department of Vascular Surgery, St. Mary's Hospital, London, UK, the Departments of Immunocytochemistry and Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, University College London, London, UK

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Abstract

Objectives: Urinary bladder hypertrophy and hyperplasia are common features of bladder outlet obstruction (BOO). The urinary bladder is known to synthesize endothelin-1 (ET-1), which is a potent vasoconstrictor peptide with mitogenic properties. Using an animal model of partial BOO, we investigated the potential role of ET-1 and its receptor subtypes (ETA and ETB) in bladder smooth muscle cell (SMC) proliferation. Materials and methods: Partial BOO was produced in adult male New Zealand White rabbits. After 3 weeks, the bladder was removed and SMCs from the dome and bladder neck were grown using standard explant methodology. At passage 2, the cells were made quiescent and then further incubated in foetal calf serum (FCS), control age-matched rabbit serum (CRS) or partial BOO serum (BRS) in the presence or absence of ETA-antagonist (BQ123) or ETB-antagonist (BQ788). SMC proliferation was then measured 24 h later with 5-bromo-2'deoxy-uracil and by cell counting using a haemocytometer at 48 h. Immunostaining for alpha-actin was performed on detrusor and bladder neck cells to confirm the presence of smooth muscle cells. Results: BQ123 and BQ788 did not influence detrusor or bladder neck SMC proliferation in FCS or CRS. However, in the presence of BRS, BQ123 and BQ788 (100 nmol/L) significantly (p = 0.008) inhibited detrusor and bladder neck SMC proliferation. Cell counts were significantly reduced from the detrusor (p = 0.03, p = 0.01 with BQ123 and BQ788, respectively) and bladder neck (p = 0.01 for both BQ123 and BQ78). Conclusions: These results suggest that ET antagonists may have a role in preventing SMC hyperplasia associated with partial BOO.

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Possible Role of Endothelin-1 in the Rabbit Urinary Bladder Hyperplasia Secondary to Partial Bladder Outlet Obstruction

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Possible Role of Endothelin-1 in the Rabbit Urinary Bladder Hyperplasia Secondary to Partial Bladder Outlet Obstruction

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