Login to Access Video or Poster Abstract: MP81-11
Sources of Funding: None

Introduction

Erectile dysfunction (ED) is a frequent complication of radical prostatectomy (RP), with penile neuropathy contributing to the disease process. Angiotensin-II is a known mediator of smooth muscle vasoconstriction and fibrosis after bilateral cavernosal nerve injury (CNI). Sacubitril-valsartan (Entresto®-Novartis), described as an angiotensin receptor neprilysin inhibitor, is a new oral drug combination for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. The aim of this study was to compare the combined effects of sacubitril/valsartan and valsartan/ sildenafil on bilateral CNI-induced functional changes in rat cavernosal tissue.

Methods

Bilateral CNI was produced in anesthetized male rats and cavernosal tissue was removed 2 weeks after CNI. Organ-bath relaxant responses were performed on corpus cavernosum (CC) strips (1×1×6 mm). After phenylephrine-induced contraction (Phe, 10 µM), dose-response curves were evaluated for valsartan (10 nM-0.5 mM), sacubitril (10 nM-0.2 mM), sacubitril/valsartan (10 nM-0.5 mM) and valsartan (10 µM)/ sildenafil (10 µM). Electrical field stimulation (EFS; duration: 15 sec amplitude: 50-80 V; frequency: 1-20 Hz; pulse width: 5msec) of the cavernosal autonomic nerves was accomplished by the use of platinum electrodes positioned on the either side of the tissue strip in the absence and presence of these drugs.

Results

Valsartan, sacubitril, and sacubitril/valsartan inhibited Phe-evoked CC contractions (maximum relaxation responses: 88.6 ± 8.4; 12.6 ± 5.9; 96.5 ± 3.5 %, respectively) in a dose-dependent manner in CC strips from CNI rats. Sildenafil-induced relaxation (50.5± 5.5 %, at 10µM) was increased by 44.5% in the presence of valsartan (91.0 ± 3.5 %, p=0.0142). EFS-induced relaxation responses (28.8 ± 3.0%, at 20Hz) occurred after Phe-precontraction potentiated by 40.8%, in the presence of valsartan (70.3 ± 6.5 %, p=0.0199).

Conclusions

Valsartan markedly relaxed isolated CC strips from CNI rats. Combining the sildenafil with valsartan causes greater nitrergic relaxation of CC smooth muscle compared to sildenafil alone. In vitro administration of valsartan combined with sacubitril in the setting of CNI may mitigate ED caused by CNI. Further experimental and clinical studies are required to advance knowledge of combined treatment modality in ED after RP.

Funding

None