Stimulation of dna synthesis in rabbit bladder wall after partial outlet obstruction and acute overdistension

Abstract

Partial outlet obstruction of the rabbit urethrovesical junction (UVJ) has been used to induce pathology in the urinary bladder characteristic of obstructive damage observed in humans. The purpose of the experiments reported here was to compare the 3H-thymidine (3H-TdR) labelling 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 3H-TdR at a dose of 0.5 microCi/g body weight. An additional 4 were overdistended to volumes 120% of maximum intravesical pressure, immediately emptied via the catheter, and injected with 3H-TdR 24 hr (1D) later. All animals were sacrificed up to 3.5 hr after injection of the label. DNA-associated radioactivity reached a peak at 3D after obstruction and was reduced substantially by 5D, although the level of incorporation remained well above control levels out to 21D. Levels of 3H-TdR incorporation 1D after overdistension bladders were about half of that found 1D following partial obstruction. The distribution of 3H-TdR labelled DNA in tissues was demonstrated by radioautography of histologic sections. One day following obstruction, 3H-Tdr incorporation was localized in the urothelium. Labelling of urothelium subsequent to 1D was reduced but remained above control levels until 21D. Labelled smooth muscle nuclei were observed only in control and 3D bladders, and they were measured at similar frequencies. Labelling of both intrinsic connective tissue (ICT) (mucosal, submucosal, and mural) and extrinsic connective tissue (ECT) (serosal) peaked at 3D after obstruction and declined thereafter but not to control levels. Labelling of ECT was, of course, limited to those bladders in which ECT was present (i.e., 3-21D). While the distribution of labelled cells in radioautograms was more variable 1D after obstruction than 1D after overdistension, the general cellular and biochemical responses to overdistension, as measured by DNA synthesis, are similar to those observed after partial outlet obstruction. Since the first sequela of obstruction is acute distension, these data support the assertion that the initial overdistension of the bladder initiates the cellular response to obstruction.