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The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase (AC) system and the cGMP/guanylate cyclase (GC) system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide (NO) leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil's actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology (ART) programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility.

In the light of increasing evidence that benign prostatic hyperplasia is associated with cardiovascular disease, we have investigated the relationship between prostatic blood flow and prostatic hyperplasia in the spontaneously-hypertensive-rat (SHR). Twelve-week-old male SHRs were treated with nicorandil for six weeks. Wistar-Kyoto rats were used as controls. Six weeks after nicorandil treatment, blood pressure and the prostatic blood flow were estimated, and tissue levels of malondialdehyde, HIF-1α, TGF-β1, bFGF, dihydrotestosterone, and α-SMA were measured. SHRs showed significant increases in blood pressure, tissue levels of malondialdehyde, HIF-1α, TGF-β1, bFGF, α-SMA and a significant decrease in the prostatic blood flow. Although treatment with nicorandil failed to alter the blood-pressure and α-SMA, it significantly ameliorated the increased levels of malondialdehyde, HIF-1α, TGF-β1, and bFGF. There were no significant differences in tissue levels of dihydrotestosterone among any groups. These data indicate that development of prostatic hyperplasia may be associated with prostatic hypoxia, which nicorandil prevents via its effect to increase the blood flow.

Testicular torsion is a common urological emergency among adolescent boys and young men. Rotation of the testis and twisting of the spermatic cord rapidly leads to ischemia, resulting in a loss of germ cells. Thus, prompt diagnosis and urgent surgical intervention are required, but the subsequent release of the torsion induces reperfusion injury, which causes further damage to the ischemic testis. Testicular torsion -detorsion (ischemia-reperfusion) injury triggers the generation of reactive oxygen species, pro-inflammatory cytokines, neutrophil recruitment, lipid peroxidation, anoxia and apoptosis, which carry a significant risk of subsequent infertility. Previously, the effects of numerous pharmacological agents and treatments have been evaluated to prevent testicular ischemia-reperfusion injury in animal models. We propose a new treatment, especially postconditioning, to prevent adverse effects of ischemiareperfusion injury after testicular torsion-detorsion.

What's known on the subject? and What does the study add? Recently, several studies have suggested that detrusor overactivity (DO) is the result of bladder ischaemia. Hypertension could affect pelvic arterial blood flow, resulting in loss of smooth muscle in the bladder with resultant loss of bladder compliance. Spontaneously hypertensive rats are considered a valuable tool for exploring the pathogenesis of DO. Some reports indicate that α1 adrenoceptor antagonists improve chronic ischaemia of the lower urinary tract in patients with LUTS, with concomitant improvement of their symptoms as well as improvement of DO through an increased bladder blood flow (BBF) in the rat with bladder outlet obstruction. However, the mechanism of improvement of silodosin on storage or irritative symptoms is not well investigated and is still unclear. Silodosin prevents hypertension‐related DO in the SHR via several possible mechanisms. One possible mechanism of the efficacy of silodosin to the DO includes the improvement of the BBF. OBJECTIVE To investigate the effect of the α1A selective adrenoceptor antagonist, silodosin, on hypertension‐related detrusor overactivity (DO) and its possible mechanism in spontaneously hypertensive rats (SHRs). MATERIALS AND METHODS Twelve‐week‐old male SHRs received treatment with silodosin (100 µg/kg perorally) once daily for 6 weeks; vehicle‐treated Wistar rats and vehicle‐treated SHRs were used for our study. Six weeks after silodosin treatment, voiding functions were estimated by voiding behaviour and cystometric studies in all groups. The bladder blood flow was measured by the hydrogen clearance method, and tissue levels of nerve growth factor (NGF) and calcitonin gene‐related peptide (CGRP) were measured by enzyme‐linked immunosorbent assay (ELISA). Furthermore, the expressions of α1 adrenoceptor subtype mRNAs in the bladder were investigated by real‐time PCR method. RESULTS The SHRs showed significant increases in blood pressure, micturition frequency and tissue levels of NGF and CGRP in the bladder. Moreover, the SHRs showed significant decreases in bladder blood flow and single voided volume estimated by both voiding behaviour and cystometric studies compared with those in the Wistar rats. Six weeks of treatment with silodosin significantly ameliorated hypertension‐related alterations of these variables with concomitant small changes of blood pressure. The expression levels of α1 adrenoceptor subtype mRNAs in the bladder were similar in all the groups and the rank order was α1A =α1D > α1B in all groups. However, there were no significant differences in the expressions of α1A adrenoceptor mRNAs between any groups. CONCLUSION The data in the present study suggest that silodosin normalizes hypertension‐related DO in SHRs, which could be related to its effect on the increased blood flow in the bladder.

These data indicate that nicorandil prevents hypertension-related bladder dysfunction in the SHR, which may be related to its effect on the increased blood flow in the bladder.

Study Type – Therapy (RCT)
Level of Evidence 1b OBJECTIVE To evaluate the effects of phosphodiesterase‐5 inhibitors (PDE5‐i) on Leydig cell secretory function (LCSF). PATIENTS AND METHODS In all, 75 men with oligoasthenospermia were treated daily for 12 weeks with either vardenafil (23 men, group A), sildenafil (25 men, group B) or l‐carnitine (26 men, group C); a further group of 22 men with oligoasthenospermia (group D) received no treatment. Serum levels of insulin‐like‐3 peptide (INSL3) were evaluated before and after the end of the treatment in each of groups A, B and C, respectively. Serum INSL3 levels were measured in each participant of group D before and after the 12‐week experimental period. RESULTS Within group A and B, the peripheral serum mean INSL3 concentration, sperm concentration, percentage of motile spermatozoa, and percentage of morphologically normal spermatozoa were significantly greater after PDE5‐i treatment than before. CONCLUSION We suggest that PDE5‐i enhances LCSF, as the mean INSL3 concentration was significantly greater after PDE5‐i administration than before, within groups A and B. This enhancement in LCSF might contribute to the increase in sperm concentration and sperm motility after administration of PDE5‐i.

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