We used a novel time-lapse imaging technique in combination with classical morphological studies to visualize and compare the effects of two currently prescribed classes of drugs used for the management of the lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH)(PDE5 inhibitors and alpha1-adrenergic receptor blockers) on intact prostatic ducts and seminal vesicles in the rat.

BPH is characterized by an enlargement of prostate tissue associated with increased smooth muscle tone. One of the most viable treatment option for patients suffering from BPH is tamsulosin, an alpha1-adrenergic receptor blocker used to relax smooth muscle cells (SMCs). Inhibitors of phosphodiesterase type 5 (PDE5) such as sildenafil or tadalafil also relax SMCs and have emerged as alternative treatment options. The prostate consists of single glands which produce the prostatic fluid. Excretory ducts transport the fluid to the urethra during the emission phase of ejaculation. Structural and functional data of glands and ducts as well as information on the response to drugs are sparse.

PDE5 was localized to the SMCs of prostate ducts. Effects of PDE5 inhibitors (sildenafil, tadalafil) and alpha1-adrenergic receptor blockers (tamsulosin) on contractile function of the prostate could be directly visualized by time-lapse imaging.
 
Excretory ducts, in contrast to glands, did not contract spontaneously. Imitating the contribution of the prostate to ejaculation by application of noradrenaline, we found that predominantly ductal SMCs ensure expulsion of secretions. Noradrenaline-induced contractions of the isolated duct segments occurred irrespective of pre-treatment with PDE5 inhibitors (sildenafil: n=6, p=0.6986 and tadalafil: n=5, p=0.3660). In both cases, the effect of noradrenaline was the same. Pre-treatment with tamsulosin, however, showed a significant reduction (n=6, p= 0.0019) of noradrenaline-induced contractions of the duct. Comparable results were obtained for seminal vesicles. Contractions (n=7, p=0,4338) and weight changes (n=7, p=0,1094) showed that PDE5 inhibitors did not interfere in the expulsion of secrete compared to control while pre-treatment with tamsulosin resulted in an absence of contractions (n=6, p=0,0082) and therefore of secretion and weight changes compared to control (n=6, p=0,0014).

Mechanistic data to support the use of PDE5 inhibitors in clinical practice for the treatment of BPH is sparse. We have demonstrated that the use of PDE5 inhibitors do not interfere with the emission phase of ejaculation in the observed tissues but alpha1-adrenergic receptor blockers do. Another tissue involved in the emission phase of ejaculation, the caudal part of the epididymis, which stores the matured sperm, is yet to be investigated.
This data perhaps explains why alpha1-adrenergic receptor blockers differ to PDE5 inhibitors by disturbing prostate and seminal vesicle secretion during the emission phase of ejaculation while still both relax SMC’s.

Data suggest that PDE5 inhibitors do not disturb expulsion of prostate and seminal vesicle secretions during ejaculation and contribute to explain adverse effects on ejaculation observed with alpha1-adrenergic receptor blockers.

Kügler R*, Mietens A*, Seidensticker M*, Tasch S, Wagenlehner FM, Kaschtanow A, Tjahjono Y, Tomczyk CU, Beyer D, Risbridger GP, Exintaris B, Ellem SJ, Middendorff R:Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects, FASEB J. 2017 Oct 31doi: 10.1096/fj.201700430R, *equal contribution