An Early Molecular Response Induced by Acute Overdistension of the Rabbit Urinary Bladder

In the rabbit, partial urinary bladder outlet obstruction rapidly increases bladder mass and alters several parameters of normal bladder function. Previous experiments on this animal model (Buttyan et al. Neurourol. Urodyn. 11:225-238, 1992) had identified an early molecular response to partial outlet obstruction that involved the profound induction of mRNA encoding a heat-shock gene, hsp-70, as well as induced expression of mRNA for basic fibroblast growth factor and certain protooncogenes. Numerous physiological studies of the hypertrophied rabbit bladder indicate that the primary stimulus for bladder growth may be the initial overdistension that occurs as the bladder fills following partial outlet obstruction. The present study was undertaken to determine if the sequence and characteristics of gene activation during the recovery following a brief period of overdistension of the rabbit bladder are comparable with the gene activity previously described in association with partial outlet obstruction. Rabbit bladders were overdistended to 20% above capacity for 1 hr and then relieved. Bladders were recovered from control (untreated) rabbits and from rabbits at 1 hr or at 1, 3 or 5 days following relief of overdistension. RNAs extracted from these tissues were examined by Northern blot assays for a number of different mRNA transcripts previously shown to be altered by partial outlet obstruction. By 1 hr following the relief from acute overdistension, there was already a greater than 10-fold increase in the expression of hsp-70 related transcripts as well as a marked increase in the expression of mRNA encoding bFGF and decreased expression of TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)