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

Background Although 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. Aim To evaluate in normal rats the possible effects of tadalafil on spontaneous seminal emission (SSE) and seminal contraction evoked by hypogastric nerve stimulation. Methods Male 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 Measure The number and weight of the ejaculatory plugs produced by corset-fitted rats and the intraluminal pressure of the seminal vesicle were evaluated. Results Tadalafil 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 Implications Tadalafil can be a treatment option in cases where there is concern about negative effects on seminal emission. Strengths and Limitations We 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. Conclusion Tadalafil 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.

Characteristics of α1‐adrenoceptor antagonists‐induced ejaculatory dysfunction on spontaneous seminal emission in rats

“…In our study, the selective α 1D ‐AR antagonist BMY7378 did not affect SSE, suggesting that the use of drugs with a high affinity for α 1A ‐AR in particular caused EjD. These results were supported by previous reports that showed silodosin, a highly selective α 1A ‐AR antagonist, can suppress SSE more strongly than tamsulosin and naftopidil 25 . In addition, silodosin had been shown to cause EjD most frequently compared to other α 1 ‐AR antagonists in clinical trials 9,21 .…”

“…These results were supported by previous reports that showed silodosin, a highly selective α 1A -AR antagonist, can suppress SSE more strongly than tamsulosin and naftopidil. 25 In addition, silodosin had been shown to cause EjD most frequently compared to other α 1 -AR antagonists in clinical trials. 9,21 Together, these findings suggested that affinity for the α 1A -AR plays an important role in EjD.…”

A phosphodiesterase 5 inhibitor, tadalafil, suppresses stromal predominance and inflammation in a rat model of nonbacterial prostatitis

“…According to these reports, in this study we used tadalafil at 10 mg/kg/day for 30 days. Recently Yoshinaga et al [25] reported that C max values of 68.5 and 460 ng/ml in rats after single oral doses of tadalafil of 2 and 10 mg/kg, respectively are physiologically relevant with the clinical plasma concentration of tadalafil is 95.6 ng/ml when the drug is administered at 5 mg/person (for BPH patients) and 446 ng/ml when it is administered at 40 mg/person (for PAH patients). Since the doses of tadalafil used in current studies are similar to the plasma concentrations in humans being treated for BPH and PAH, the results we showed in the paper partly may explain the protective mechanisms of Tadalafil in BPH patients.…”