Molecular aspects of bladder outlet obstruction.

In an animal model of obstruction, increasing load induces significant smooth muscle hypertrophy which is associated with a down-regulation of myosin heavy chain expression. This undoubtedly contributes to the decreased smooth muscle contractility seen in this model. Moreover, obstruction-induced hypertrophy leads to the development of a dedifferentiated smooth muscle phenotype, as evidenced by a revision of the cell to fetal (of non-muscle) gene expression patterns. Similar alterations are seen in atherosclerotic vessels and other pathologic smooth muscle systems. In these systems, dedifferentiation is also associated with significant alterations in extracellular matrix expression. It seems likely that obstruction in the bladder induces dedifferentiation of the smooth muscle cell which alters contractility as well as extracellular matrix expression, leading to altered bladder performance and decreased compliance.