finrozole and Urethral-Obstruction

We treat neonatally estrogenized rats and aromatase over expressing AROM+ male mice with infravesical obstruction using the specific aromatase inhibitors finrozole and letrozole, and analyzed whether developmentally induced alterations in urodynamics and rhabdosphincter are reversible in adulthood.. Adult estrogenized rats and AROM+ mice were treated with aromatase inhibitors for 6 weeks. Maximal and mean bladder pressure, the urinary flow rates and electromyography activity were recorded from the proximal rhabdosphincter. In addition, proximal rhabdosphincter thickness in the AROM+ mouse was measured and correlated with seminal vesicle size and serum testosterone concentrations.. Finrozole and/or letrozole treatment significantly increased the mean maximal flow rate plus or minus SD in AROM+ mice (4.7 +/- 2.0 versus 13.3 +/- 4.4 ml. per minute, p = 0.0004) and in estrogenized rats (18.4 +/- 6.18 versus 31.1 +/- 10.85 ml. per minute for finrozole p = 0.005) and 32.4 +/- 14.3 for letrozole, p = 0.005), while bladder pressure slightly decreased. The reappearance of transient repolarization, indicating urethral lumen opening, coincided with an increased flow rate on electromyography in the proximal rhabdosphincter in rats. Relative thickness of the proximal rhabdosphincter (p = 0.007), seminal vesicle size (p = 0.0002) and mean serum testosterone concentration (472.5 +/- 230.35 versus 3,065.6 +/- 1,994.67 pg./ml., p = 0.0002) were restored after finrozole treatment in AROM+ mice.. Current findings indicate that alterations in urodynamics, seminal vesicle size, and rhabdosphincter size and function in developmentally estrogenized male rodents are reversible when treated with aromatase inhibitor.

Topics: Animals; Animals, Newborn; Aromatase; Aromatase Inhibitors; Electromyography; Estrogens; Letrozole; Male; Mice; Mice, Transgenic; Nitriles; Rats; Seminal Vesicles; Testosterone; Triazoles; Urethra; Urethral Obstruction; Urodynamics