AJP - Regulatory, Integrative and Comparative Physiology, Vol 263, Issue 6 1284-R1290, Copyright © 1992 by American Physiological Society

ARTICLES

Detrusor hyperplasia and expression of "immediate early" genes with onset of abnormal urodynamic parameters

O. M. Karim, N. Seki and J. L. Mostwin
James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland 21205.

To determine the stimulus for growth of the detrusor with a pathophysiological obstruction to the urinary stream, we studied urodynamic parameters, detrusor weight, detrusor DNA content, and the expression of early growth-related protooncogenes in a model of gradual onset bladder outflow obstruction and reversal of obstruction. Silver jeweler's jump rings were placed loosely round the urethra of immature guinea pigs, allowing an obstruction to develop gradually with animal growth. At 1, 2, 4, and 8 wk after surgery, animals were killed after urodynamic studies under urethan anesthesia. Bladders were removed, and mucosa-free detrusor was weighed and frozen for assay of DNA content and expression of c-fos and c-myc protooncogenes. Results were compared with sham-operated age-matched control animals. One week after surgery there was no change in the urodynamic parameters, detrusor weight, or DNA content. At 2, 4, and 8 wk after placement of the silver rings, animals developed obstructive voiding patterns, an increase in detrusor weight, and total DNA content. The onset of obstructive voiding patterns correlated with transient increased levels of c-fos and c-myc mRNA by Northern blot analysis. Autoradiography of in vivo [methyl-3H]thymidine-labeled detrusor muscle from obstructed animals showed myocyte DNA synthesis and mitosis, implying myocyte hyperplasia. After removal of the silver ring, the obstructive voiding patterns resolved and detrusor weight and DNA content returned to levels of the control animals. These results suggest that in the guinea pig bladder subjected to a gradual onset outflow obstruction, detrusor growth is initiated by the development of obstructive voiding patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				T. S. Lendvay, R. Sweet, C.-H. Han, T. Soygur, J.-F. Cheng, J. C. Plaire, J. S. Charleston, L. B. Charleston, S. Bagai, K. Cochrane, et al. Compensatory paracrine mechanisms that define the urothelial response to injury in partial bladder outlet obstruction Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1147 - F1156. [Abstract] [Full Text] [PDF]

				M. Imamura, A. Kanematsu, S. Yamamoto, Y. Kimura, I. Kanatani, N. Ito, Y. Tabata, and O. Ogawa Basic fibroblast growth factor modulates proliferation and collagen expression in urinary bladder smooth muscle cells Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1007 - F1017. [Abstract] [Full Text] [PDF]

				D. J. Galvin, R. W. G. Watson, J. I. Gillespie, H. Brady, and J. M. Fitzpatrick Mechanical stretch regulates cell survival in human bladder smooth muscle cells in vitro Am J Physiol Renal Physiol, December 1, 2002; 283(6): F1192 - F1199. [Abstract] [Full Text] [PDF]

				J. M. Park, T. Yang, L. J. Arend, J. B. Schnermann, C. A. Peters, M. R. Freeman, and J. P. Briggs Obstruction stimulates COX-2 expression in bladder smooth muscle cells via increased mechanical stretch Am J Physiol Renal Physiol, January 1, 1999; 276(1): F129 - F136. [Abstract] [Full Text] [PDF]

				J. M. Park, J. G. Borer, M. R. Freeman, and C. A. Peters Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells Am J Physiol Cell Physiol, November 1, 1998; 275(5): C1247 - C1254. [Abstract] [Full Text] [PDF]

				J. M. Park, T. Yang, L. J. Arend, A. M. Smart, J. B. Schnermann, and J. P. Briggs Cyclooxygenase-2 is expressed in bladder during fetal development and stimulated by outlet obstruction Am J Physiol Renal Physiol, October 1, 1997; 273(4): F538 - F544. [Abstract] [Full Text] [PDF]