Dipyridamole reduces penile apoptosis in a rat model of post-prostatectomy erectile dysfunction

ABSTRACT Purpose: Despite the nerve-sparing technique, many patients suffer from erectile dysfunction after radical prostatectomy (RP) due to cavernous nerve injury. The aim of this study was to evaluate dipyridamole as a potential treatment agent of post-radical prostatectomy erectile dysfunction. Material and methods: A total of 18 male Sprague-Dawley rats were randomized into three experimental Groups (SHAM+DMSO, BCNI+DMSO and BCNI+DIP). An animal model of bilateral cavernous nerve crush injury (BCNI) was established to mimic the partial nerve damage during nerve-sparing RP. After creating of BCNI, dimethyl sulphoxide (DMSO) was administered transperitoneally as a vehicle to SHAM+DMSO and BCNI+DMSO Groups. BCNI+DIP Group received dipyiridamole (10mg/kg/day) as a solution in DMSO for 15 days. Afterwards, rats were evaluated for in vivo erectile response to cavernous nerve stimulation. Penile tissues were also analyzed biochemically for transforming growth factor-β1 (TGF-β1) level. Penile corporal apoptosis was determined by TUNEL method. Results: Erectile response was decreased in rats with BCNI and there was no significant improvement with dipyridamole treatment. TGF-β1 levels were increased in rats with BCNI and decreased with dipyridamole treatment. Dipyridamole led to reduced penile apoptosis in rats with BCNI and there was no significant difference when compared to sham operated rats. Conclusions: Although fifteen-day dipyridamole treatment has failed to improve erectile function in rats with BCNI, the decline in both TGF-β1 levels and apoptotic indices with treatment may be helpful in protecting penile morphology after cavernous nerve injury.

Dipyridamole reduces penile apoptosis in a rat model of post-prostatectomy erectile dysfunction.

PURPOSE: Despite the nerve-sparing technique, many patients suffer from erectile dysfunction after radical prostatectomy (RP) due to cavernous nerve injury. The aim of this study was to evaluate dipyridamole as a potential treatment agent of post-radical prostatectomy erectile dysfunction. MATERIAL AND METHODS: A total of 18 male Sprague-Dawley rats were randomized into three experimental Groups (SHAM+DMSO, BCNI+DMSO and BCNI+DIP). An animal model of bilateral cavernous nerve crush injury (BCNI) was established to mimic the partial nerve damage during nerve-sparing RP. After creating of BCNI, dimethyl sulphoxide (DMSO) was administered transperitoneally as a vehicle to SHAM+DMSO and BCNI+DMSO Groups. BCNI+DIP Group received dipyiridamole (10mg/kg/day) as a solution in DMSO for 15 days. Afterwards, rats were evaluated for in vivo erectile response to cavernous nerve stimulation. Penile tissues were also analyzed biochemically for transforming growth factor-ß1 (TGF-ß1) level. Penile corporal apoptosis was determined by TUNEL method. RESULTS: Erectile response was decreased in rats with BCNI and there was no significant improvement with dipyridamole treatment. TGF-ß1 levels were increased in rats with BCNI and decreased with dipyridamole treatment. Dipyridamole led to reduced penile apoptosis in rats with BCNI and there was no significant difference when compared to sham operated rats. CONCLUSIONS: Although fifteen-day dipyridamole treatment has failed to improve erectile function in rats with BCNI, the decline in both TGF-ß1 levels and apoptotic indices with treatment may be helpful in protecting penile morphology after cavernous nerve injury.

Effect of doxazosin on expression of eNOS in rat kidney in the presence of partial bladder outlet obstruction.

BACKGROUND: The role of nitric oxide in the pathogenesis of renal injury has begun to be appreciated. We therefore designed this study to demonstrate the relationship between endothelial nitric oxide synthase (eNOS) expression and doxazosin in the kidneys of rats with surgically created partial bladder outlet obstruction (BOO), to further understand the role of doxazosin in the prevention of renal parenchymal damage by partial BOO. MATERIAL AND METHODS: A total of 35 adult female Wistar rats, mean weight 250 g, were randomly allocated to 3 experimental groups: group1, sham-operated (n=10); group 2, partial BOO group (n=14) and group 3, partial BOO group treated with doxazosin (n=11). Partial BOO in rats was surgically induced. Results were assessed by eNOS immunohistochemistry. RESULTS: eNOS staining in kidneys in group 1 (16.45 ± 1.63) was significantly higher than in group 2 (5.09 ± 0.61) (p<0.05). After 15 days of doxazosin treatment in addition to partial BOO (group 3), eNOS staining in the kidney (11.80 ± 1.63) was significantly higher than in group 2 (5.09 ± 0.61) (p<0.05). In samples taken after 15 days of doxazosin treatment in addition to partial BOO, eNOS staining in kidneys (11.80 ± 1.63) was lower than in the sham-operated group (16.45 ± 1.63), but the difference was not significant (p>0.05). CONCLUSION: These findings may provide insight into the beneficial and restorative effects of α(1)-adrenoceptor antagonists on eNOS expression in the kidney, when used to treat symptoms of benign prostate hyperplasia and hypertension.