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, w hich may affect up to 10 million Americans; this may cost over 10 bill ion dollars to manage through either surgery, medical products, drugs, or the expense of nursing home placement. Cardiac pharmacology has ha d many years of major funding either at the federal level or via the p harmaceutic industry in the development of its current armamentarium. Given the prevalence, morbidity, and mortality of cardiovascular disea se, this was a logical progression. In contrast, the urologic pharmaco poeia has lagged behind in part because of a lag in long-term investme nt 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 medic al options for pharmacologic manipulation of the lower urinary tract d emands a better understanding of how the smooth muscle operates at a p hysiologic, pharmacologic, cellular, and molecular level. As urologist s we face several dilemmas with regard to bladder function: 1. How doe s bladder compliance change with normal development? 2. How does bladd er contractility change with normal development? 3. How does the bladd er's contractile response change following outlet obstruction? 4. At w hat point does outlet obstruction alter the bladder's passive properti es? 5. Are there markers that can predict the recovery of detrusor fun ction after outlet obstruction has been surgically relieved? 6. If nor mal function is not restored by surgical reversal of outlet obstructio n, then what medical regimens might be employed to enhance the bladder function? 7. If one is going to observe patients with benign prostati c hyperplasia (BPH) over the long term, are there predictors of irreve rsible detrusor dysfunction?