UPDATE ON BLADDER SMOOTH-MUSCLE PHYSIOLOGY

The urinary bladder responds to distension induced by a number of diff erent stresses with rapid and substantial increases in bladder mass an d concomitant alterations in the contractile responses to neuronal sti mulation, pharmacological simulation by autonomic agonists, and membra ne depolarization. Furosemide, sucrose, or diabetes-induced diuresis, as well as outlet obstruction and overdistension all produce similar e ffects on the bladder. Accompanying the increases in bladder mass and contractile changes are increases in DNA synthesis and [H-3]- thymidin e uptake. Autoradiographic studies have localized the increased DNA sy nthesis following bladder distension initially to the urothelium, foll owed by slower increases in labelling of the lamina propria and extram ural connective tissue. The net result of these compartmental differen ces in DNA synthesis is a reorganization of the structural relationshi ps between smooth-muscle cells, the connective-tissue matrix, and the extrinsic connective-tissue lamina. This may contribute to the functio nal changes which occur after severe overdistension. Increases in the expression of heat-shock protein-70, basic fibroblast growth factor, N -ras, and c-myc, and decreases in transforming growth factor-beta occu rred acutely after obstruction, suggesting that these changes may play a role in obstruction-induced bladder hypertrophy. Removal of the obs truction induces apoptosis of urothelial and connective tissue element s in the bladder, accompanied by increases in transforming growth fact or-beta and decreases in basic fibroblast growth factor genes, and a r eversal of the bladder dysfunction. Therefore the bladder hyperplasia after outlet obstruction and the regression following removal of the o bstruction seem to be directly opposing processes governed by gene exp ression.