Mechanisms of bladder smooth-muscle hypertrophy and decompensation: lessons from normal development and the response to outlet obstruction

A major clinical issue facing the urologist is urinary incontinence, which may affect up to 10 million Americans; this may cost over 10 billion dollars to manage through either surgery, medical products, drugs, or the expense of nursing home placement. Cardiac pharmacology has had many years of major funding either at the federal level or via the pharmaceutic industry in the development of its current armamentarium. Given the prevalence, morbidity, and mortality of cardiovascular disease, this was a logical progression. In contrast, the urologic pharmacopoeia has lagged behind in part because of a lag in long-term investment in this area. Many of the medications we use in an effort to affect bladder performance are 20-30 years old. The development of new medical options for pharmacologic manipulation of the lower urinary tract demands a better understanding of how the smooth muscle operates at a physiologic, pharmacologic, cellular, and molecular level. As urologists we face several dilemmas with regard to bladder function: 1. How does bladder compliance change with normal development? 2. How does bladder contractility change with normal development? 3. How does the bladder's contractile response change following outlet obstruction? 4. At what point does outlet obstruction alter the bladder's passive properties? 5. Are there markers that can predict the recovery of detrusor function after outlet obstruction has been surgically relieved? 6. If normal function is not restored by surgical reversal of outlet obstruction, then what medical regimens might be employed to enhance the bladder function? 7. If one is going to observe patients with benign prostatic hyperplasia (BPH) over the long term, are there predictors of irreversible detrusor dysfunction?