caa a22 4500 475742680 CHVBK 20180406123504.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s002400000115 doi (NATIONALLICENCE)springer-10.1007/s002400000115 Inhibition of diabetic bladder smooth muscle cell proliferation by endothelin receptor antagonists [Elektronische Daten] [F. H. Mumtaz, N. Shukla, M. E. Sullivan, C. S. Thompson, M. A. Khan, R. J. Morgan, G. Stansby, D. P. Mikhailidis] Urinary bladder hypertrophy and hyperplasia are well recognised in diabetic cystopathy. The urinary bladder is known to synthesise endothelin-1 (ET-1), a potent vasoconstrictor peptide with mitogenic properties. Using diabetic New Zealand White (NZW) rabbits, we investigated the potential role of ET receptor subtypes (ETA and ETB) on the proliferation of bladder smooth muscle cells (SMC). Diabetes mellitus was induced in adult male NZW rabbits. After 6 months, control (n=6) and diabetic (n=6) bladders were removed and SMC from the dome and bladder neck were grown using standard explant methodology. At passage two, the cells were made quiescent and then further incubated in foetal calf serum (FCS), control age-matched rabbit serum (CRS) or diabetic rabbit serum (DRS) in the presence or absence of ETA-antagonist (BQ123) or ETB-antagonist (BQ788). SMC proliferation was then measured with 5-bromo-2′deoxy-uracil 24 h later and by cell counting (using a haemocytometer) at 48 h. Neither BQ123 nor BQ788 influenced detrusor or bladder neck SMC proliferation in FCS or CRS. However, in the presence of DRS, BQ123 and BQ788 significantly inhibited diabetic detrusor and bladder neck SMC proliferation at 30 and 100 nmol/l (P < 0.03 and P < 0.01, respectively). Cell counts were also significantly reduced from the diabetic detrusor and bladder neck (P < 0.01 and P < 0.03 with BQ123 and BQ788, respectively). These results suggest that ET may play a pathophysiological role in the bladder SMC hyperplasia associated with diabetes mellitus. Springer-Verlag Berlin Heidelberg, 2000 Key words Endothelin-1 nationallicence Rabbit nationallicence Bladder nationallicence Diabetes mellitus nationallicence Smooth muscle cell proliferation nationallicence Mumtaz F. H. Department of Urology, Royal Free Hospital, PondStreet, London NW3 2QG, UK, GB aut Shukla N. Department of Vascular Surgery, St Mary's Hospital, London, UK, GB aut Sullivan M. E. Department of Urology, Royal Free Hospital, PondStreet, London NW3 2QG, UK, GB aut Thompson C. S. Departments of Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School (Royal Free campus), University College London, UK, GB aut Khan M. A. Department of Urology, Royal Free Hospital, PondStreet, London NW3 2QG, UK, GB aut Morgan R. J. Department of Urology, Royal Free Hospital, PondStreet, London NW3 2QG, UK, GB aut Stansby G. Department of Vascular Surgery, St Mary's Hospital, London, UK, GB aut Mikhailidis D. P. Department of Urology, Royal Free Hospital, PondStreet, London NW3 2QG, UK, GB aut https://doi.org/10.1007/s002400000115 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002400000115 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mumtaz F. H. Department of Urology, Royal Free Hospital, PondStreet, London NW3 2QG, UK, GB aut NATIONALLICENCE 700 1- Shukla N. Department of Vascular Surgery, St Mary's Hospital, London, UK, GB aut NATIONALLICENCE 700 1- Sullivan M. E. Department of Urology, Royal Free Hospital, PondStreet, London NW3 2QG, UK, GB aut NATIONALLICENCE 700 1- Thompson C. S. Departments of Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School (Royal Free campus), University College London, UK, GB aut NATIONALLICENCE 700 1- Khan M. A. Department of Urology, Royal Free Hospital, PondStreet, London NW3 2QG, UK, GB aut NATIONALLICENCE 700 1- Morgan R. J. Department of Urology, Royal Free Hospital, PondStreet, London NW3 2QG, UK, GB aut NATIONALLICENCE 700 1- Stansby G. Department of Vascular Surgery, St Mary's Hospital, London, UK, GB aut NATIONALLICENCE 700 1- Mikhailidis D. P. Department of Urology, Royal Free Hospital, PondStreet, London NW3 2QG, UK, GB aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer