Comparison of the Effects of Tadalafil and α1-Adrenoceptor Antagonists on Spontaneous Seminal Emission and Electrical Field Stimulation-Induced Seminal Vesicle Contraction in Rats

Abstract

BackgroundAlthough numerous reports have shown that α1-adrenoceptor (α1-AR) antagonists, which are used to treat benign prostatic hyperplasia (BPH), can cause ejaculatory disorders, few studies have investigated whether the phosphodiesterase 5 (PDE5) inhibitor tadalafil has such adverse effects. In this study, we compared the effects of tadalafil and α1-AR antagonists on seminal emission and their mechanisms of action. AimTo evaluate in normal rats the possible effects of tadalafil on spontaneous seminal emission (SSE) and seminal contraction evoked by hypogastric nerve stimulation. MethodsMale Sprague-Dawley rats were used. To assess SSE, plastic corsets were fitted around the thorax and upper abdomen of male Sprague–Dawley rats to prevent genital autogrooming. Rats were treated orally with tadalafil or an α1-AR antagonist (silodosin, naftopidil, or tamsulosin) for 3 days and housed in wire-bottomed cages. Ejaculatory plugs dropped on the bottoms of the cages were counted and weighed. To assess the intraluminal pressure of seminal vesicles, the hypogastric nerve of urethane-anesthetized rats was isolated and electrically stimulated. After stabilization of seminal vesicle contraction, the rats were intravenously administered test drugs. The expression of PDE5, endothelial nitric oxide synthetase (eNOS), and neuronal NOS (nNOS) in the seminal vesicle and vas deferens were measured by reverse-transcription polymerase chain reaction. Main Outcome MeasureThe number and weight of the ejaculatory plugs produced by corset-fitted rats and the intraluminal pressure of the seminal vesicle were evaluated. ResultsTadalafil did not affect the number or weight of the ejaculatory plugs of corset-fitted rats, whereas all α1-AR antagonists decreased both in a dose-dependent manner. The α1-AR antagonists, but not tadalafil, inhibited the seminal vesicle contraction evoked by electrical stimulation of the hypogastric nerve. The seminal vesicle and vas deferens expressed higher levels of PDE5 and eNOS mRNA and lower levels of nNOS mRNA relative to the urethra. Clinical ImplicationsTadalafil can be a treatment option in cases where there is concern about negative effects on seminal emission. Strengths and LimitationsWe demonstrated different effects of tadalafil and 3 α1-AR antagonists on rat SSE and their mechanisms of action by measuring seminal vesicle contractility in vivo. A limitation is that we used normal rats, not BPH model rats, and so our results might not apply to human BPH patients. ConclusionTadalafil did not inhibit spontaneous seminal emission or electrical field stimulation–induced seminal vesicle contraction in normal rats. The NO–cyclic guanosine monophosphate pathway is unlikely to be involved in the inhibition of seminal vesicle contraction in normal rats.Yoshinaga R, Fukui T, Yoshifuji M, et al. Comparison of the Effects of Tadalafil and α1-Adrenoceptor Antagonists on Spontaneous Seminal Emission and Electrical Field Stimulation-Induced Seminal Vesicle Contraction in Rats. J Sex Med 2019;16:680–690.