TIME-DEPENDENT REMODELING OF THE BLADDER WALL IN GROWING RABBITS AFTER PARTIAL OUTLET OBSTRUCTION

Purpose: We asked whether a urethral constriction gradually developed during growth would give rise to a structural remodeling of the bladde r wall distinct from that of the mature rabbits in terms of cellular r esponse. Materials and Methods: We examined the serosa and detrusor mu scle in immature rabbits whose urethra was obstructed at 30 days postn atal and studied 7 to 30 days after partial outlet obstruction. Morpho metry, bromo-deoxyuridine (BrdU) incorporation, Western blotting and i mmunocytochemical staining with a panel of monoclonal antibodies speci fic to selected cytoskeletal, cytocontractile and membrane-related pro teins unique to non-muscle and smooth muscle cells (SMC) were used to analyze the effects of obstruction on the differentiation pattern. Res ults: In comparison with results in adult obstructed bladders, we have found that in growing rabbits: (1) the cell conversion from fibroblas ts to SMC, occurring within the 'extrinsic' region of serosal thickeni ng, takes place earlier; (2) newly formed SMC are localized exclusivel y to the thickened serosa, and can group in bundles depending on the d ensity of the regional innervation; (3) the peak level of BrdU incorpo ration is more elevated than in the adult bladder wall; and (4) change in the phenotypic profile of SMC of detrusor muscle is delayed. Concl usion: These data indicate that the basic features of structural remod eling in the two models are similar, though partial outlet obstruction produced in growing animals accelerates the fibroblast conversion to SMC and their spatial, differentiation-specific arrangement in the ser osa. The late phenotypic changes in obstructed detrusor muscle correla te with the decline of the DNA synthesis level after an initial burst and strongly suggest that newly formed SMC in the serosa do not derive from pre-existing SMC.