STIMULATION OF DNA-SYNTHESIS IN RABBIT BLADDER WALL AFTER PARTIAL OUTLET OBSTRUCTION AND ACUTE OVERDISTENSION

Partial outlet obstruction of the rabbit urethrovesical junction (UVJ) has been used to induce pathology in the urinary bladder characterist ic of obstructive damage observed in humans. The purpose of the experi ments reported here was to compare the H-3-thymidine (H-3-TdR) labelli ng of DNA in urinary bladders of male New Zealand White (NZW) rabbits subjected to partial outlet obstruction or overdistension. A total of 18 animals was used. Two normal controls, and 12 partially obstructed animals (at 1 day [D], 3D, 5D, 7D, 14D, and 21D) were injected (i.v.) with H-3-TdR at a dose of 0.5 mu Ci/g body weight. An additional 4 wer e overdistended to volumes 120% of maximum intravesical pressure, imme diately emptied via the catheter, and injected with H-3-TdR 24 hr (1D) later. All animals were sacrificed up to 3.5 hr after injection of th e label. DNA-associated radioactivity reached a peak at 3D after obstr uction and was reduced substantially by 5D, although the level of inco rporation remained well above control levels out to 21D. Levels of H-3 -TdR incorporation 1D after overdistension bladders were about half of that found 1D following partial obstruction. The distribution of H-3- TdR labelled DNA in tissues was demonstrated by radioautography of his tologic sections. One day following obstruction, H-3-Tdr incorporation was localized in the urothelium. Labelling of urothelium subsequent t o 1D was reduced but remained above control levels until 21D. Labelled smooth muscle nuclei were observed only in control and 3D bladders, a nd they were measured at similar frequencies. Labelling of both intrin sic connective tissue (ICT) (mucosal, submucosal, and mural) and extri nsic connective tissue (ECT) (serosal) peaked at 3D after obstruction and declined thereafter but not to control levels. Labelling of ECT wa s, of course, limited to those bladders in which ECT was present (i.e. , 3-21D). While the distribution of labelled cells in radioautograms w as more variable 1D after obstruction than 1D after overdistension, th e general cellular and biochemical responses to overdistension, as mea sured by DNA synthesis, are similar to those observed after partial ou tlet obstruction. Since the first sequela of obstruction is acute dist ension, these data support the assertion that the initial overdistensi on of the bladder initiates the cellular response to obstruction. (C) 1994 Wiley-Liss, Inc.