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.

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.

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BACKGROUND AND PURPOSENicorandil, an ATP-sensitive potassium (KATP) channel opener and nitric oxide donor, is used in the treatment of angina and acute heart failure. Here we investigated the effects of two KATP channel openers, nicorandil and cromakalim on ischaemia reperfusion (I-R) injury in the kidney. EXPERIMENTAL APPROACHRight nephrectomy was performed in 8-week-old male Sprague-Dawley rats and they were then divided into six groups: control group; I-R, including 30 min of left renal ischaemia followed by 24 h of reperfusion; I-R groups plus nicorandil 3 or 10 mg·kg -1 i.p.; and I-R groups plus cromakalim 100 or 300 mg·kg -1 i.p. After reperfusion, renal function was estimated by serum creatinine (SCr), urinary albumin : creatinine ratio (ACR) and urinary b2-microglobulin (b2-MG). Levels of KATP channel subtypes were investigated by Western blot. Kidney sections were stained for 4-hydroxy-2-nonenal and 8-hydroxy-2′-deoxyguanosine. KEY RESULTSRenal I-R induced significant increases in SCr, ACR and b2-MG levels compared with the control animals. Treatment with KATP channel openers reduced urinary b2-MG levels, raised by I-R. Both KIR6.1 and KIR6.2 channels were expressed. Expression of KIR6.2 channels in the I-R group was lower than in the control group, which was restored to normal by treatment with KATP channel openers. Histologically, severe acute tubular damage was observed in the I-R kidney and this damage was ameliorated by KATP channel openers, dose-dependently. CONCLUSIONS AND IMPLICATIONSATP-sensitive potassium channel openers protected against proximal tubule damage after I-R injury. Nicorandil could represent a powerful additional component in the treatment of patients undergoing partial nephrectomy or renal transplantation. Abbreviations4-HNE, 4-hydroxy-2-nonenal; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; CKD, chronic kidney disease; ELISA, enzyme-linked immunosorbent assay; IPreC, ischaemic preconditioning; I-R, ischaemia-reperfusion; KATP channel, ATP-sensitive potassium channel; OSOM, outer stripe of outer medulla; PAS, periodic acid-Schiff; ROS, reactive oxygen species; b2-MG, b2-microglobulin

time simultaneously with a laser Doppler flowmeter and an NO-selective electrode, respectively. After death the tissue levels of NO 2 -NO 3 (a marker of NO production), malondialdehyde (a marker of lipid peroxidation), 8-hydroxydeoxyguanosine (a marker of oxidative DNA damage), myeloperoxidase (a marker of neutrophil infiltration), and heat-shock protein 70 (HSP 70) and its mRNA were measured. The testicular tissue was also analysed histologically. RESULTSClamping the testicular artery resulted in a decrease of blood flow to 0-5% of the basal level measured before clamping. NO release was increased during clamping and gradually recovered to the basal level on removing the clip. Interestingly, the peak of NO release in rats of the no-drug group occurred at the start of reperfusion, while that in the high-dose drug group occurred several minutes later. The levels of NO 2 -NO 3 , malondialdehyde, 8-hydroxydeoxyguanosine, myeloperoxidase and HSP 70 and its mRNA, and histological variables, were significantly greater in the no-drug I-R group than in the control, and these variables were ameliorated by treatment with edaravone. CONCLUSIONThese results indicate that edaravone reduces the oxidative stress and prevents the testicular damage induced by I-R.