FK1706 enhances the recovery of erectile function following bilateral cavernous nerve crush injury in the rat.
BACKGROUND
Advances in neurobiology have led to a surge of clinical interest in the development of protective and regenerative neuromodulatory strategies, as surgical therapies for prostate cancer often result in neuronal damage and debilitating loss of sexual function.


OBJECTIVE
To investigate the dose-dependent efficacy of FK1706, a nonimmunosuppressant immunophilin ligand, for the recovery of erectile function following bilateral cavernous nerve crush injury in the rat.


METHODS
Recovery of erectile function was assessed by cavernous nerve electrostimulation and reported as maximal increase of intracavernous pressure (ICP) and area under the curve (AUC). Changes in animal weights, percentage completion of treatment course, and survival were compared between groups. METHODS; Thirty-five Sprague-Dawley male rats were randomly divided into five equal groups: seven animals received a sham operation, whereas 28 animals underwent bilateral cavernous nerve crush injury, followed by subcutaneous injection of vehicle alone (1.0 mL/kg), or low (0.1 mg/kg), medium (0.32 mg/kg), or high dose (1.0 mg/kg) FK1706 5 days per week for 8 weeks.


RESULTS
Erectile dysfunction did not occur in the sham group (mean maximal ICP increase of 100.8 +/- 6.3 cmH(2)O), whereas nerve injury and vehicle treatment produced a significant reduction in ICP response to 34.4 +/- 12.8 cmH(2)O. The mean ICP increase for high-dose FK106 treatment was 73.9 +/- 6.3 cmH(2)O (P < 0.01 vs. vehicle) compared with 58.3 +/- 7.4 cmH(2)O and 56.9 +/- 8.3 for low and medium doses (P > 0.05). Similar stepwise findings were observed using AUC data. No significant maximal aortic blood pressure or weight differences occurred between groups and all animals completed treatment.


CONCLUSIONS
High-dose subcutaneous FK1706 therapy promoted recovery of erectile function following bilateral cavernous nerve crush injury in the rat. No significant differences between groups were observed for changes in weight, and the 8-week treatment course was completed for all animals.
Bella
Anthony J
AJ
Division of Urology, University of California San Francisco, San Francisco, CA, USA. abella@urology.ucsf.edu
Hayashi
Narihiko
N
Carrion
Rafael E
RE
Price
Raymond
R
Lue
Tom F
TF
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000293:injuries* / Q000294:innervation* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology*
C505380:FK1706; D016559:Tacrolimus