Calcium channel antagonists prevent urinary bladder growth and neuroplasticity following mechanical stress

Cytosolic Ca2+ has been postulated to regulate smooth muscle hypertrophy and growth factor production. Consistent with this hypothesis we report that the Ca2+ channel antagonists verapamil and diltiazem prevent bladder and neuronal growth in rats in response to 3 wk of urethral obstruction. Ca2+ channel blockers prevented 30-45% of the increase in bladder weight, protein, and DNA content found in obstructed animals. Similarly, these drugs produced a 15-27% reduction in area profiles for retrogradely labeled (Fluoro-Gold) motoneurons in the major pelvic ganglia and afferents in the L6-S1 dorsal root ganglia after obstruction. The reduced growth in neuronal areas was attributed, in part, to less nerve growth factor (NGF) in bladders of obstructed rats receiving verapamil (8.5 pg/bladder) or diltiazem (14.5 pg/bladder) compared with obstructed animals not given these drugs (58.2 pg/bladder). The alpha 1-adrenergic antagonist, prazosin, while decreasing voiding frequency in obstructed rats, had no significant impact on bladder weight or neuronal size. These reductions in the increase in bladder hypertrophy and NGF content may be due to altered handling of Ca2+.