Evaluation of combined therapeutic effects of hydrogen sulfide donor sodium hydrogen sulfide and phosphodiesterase type-5 inhibitor tadalafil on erectile dysfunction in a partially bladder outlet obstructed rat model

Abstract

Aims: To evaluate the impacts of hydrogen sulfide (H2S) donor, sodium hydrogen sulfide (NaHS), and phosphodiesterase type-5 inhibitor (PDE5i), tadalafil per se and their combination treatment on partial bladder outlet obstruction (PBOO)-induced erectile dysfunction (ED). Methods: Sprague-Dawley rats were equally divided into five groups: (a) sham-operated control; (b) PBOO; (c) PBOO-treated with NaHS (5.6 mg/kg/day, ip); (d) PBOO-treated with tadalafil (2 mg/kg/day, oral); and (e) PBOO-treated with combination of NaHS and tadalafil. The obstruction was created by urethral ligation for 6 weeks. In vivo erectile responses, in vitro relaxant and contractile responses in penile tissue as well as protein expression of nitric oxide synthases (NOS), H2S synthesis enzymes, oxidative stress, hypoxia, fibrosis markers, and the smooth muscle/collagen ratio and apoptosis were analyzed. Results: Combined treatment entirely returned increased bladder mass, reduced erectile responses, relaxation responses to acetylcholine, and electrical field stimulation in obstructed rats, while partial amelioration was observed after mono-treatment. Decreased neuronal NOS and 3-mercaptopiruvate transferase enzyme expressions in penile tissue from obstructed rats were also entirely restored by the combined treatment. Mono-treatment partially improved increased hypoxia, oxidative stress, fibrosis markers, decreased smooth muscle mass, and H2S levels, while combined therapy completely recovered. Conclusions: The combination therapy with H2S donor and PDE5i had positive effects on erectile responses through the improvement of ischemia-induced morphological and functional penile alterations in obstruction. H2S and NO may likely play a synergistic role in the regulation of erectile function and have constructive effects on clinical outcomes in male patients with ED and benign prostatic hyperplasia/lower urinary tract symptoms.