AJP - Regulatory, Integrative and Comparative Physiology, Vol 266, Issue 1 20-R26, Copyright © 1994 by American Physiological Society
Calcium channel antagonists prevent urinary bladder growth and neuroplasticity following mechanical stress
W. D. Steers, M. Albo and J. B. Tuttle
Department of Urology, University of Virginia, Charlottesville 22908.
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+.
