Vascul Pharmacol 2006 May 19; (Read article online)

Vidavalur R, Penumathsa SV, Zhan L, Thirunavukkarasu M, Maulik N

This study was undertaken to investigate the effect of phosphodiesterase-5 (PDE5) inhibitor, sildenafil, on angiogenic response in human coronary arteriolar endothelial cells (HCAEC). The cells exposed to sildenafil (1-20 muM) demonstrated significantly accelerated tubular morphogenesis with the induction of thioredoxin-1 (Trx-1), hemeoxygenase-1 (HO-1) and VEGF. Sildenafil induced VEGF and angiopoietin specific receptors such as KDR, Tie-1 and Tie-2. This angiogenic response was repressed by tinprotoporphyrin IX (SnPP), an inhibitor of HO-1 enzyme activity. Sildenafil below 1 muM has no angiogenic effect as evidenced by reduced tuborogenesis. Sildenafil along with SnPP inhibited both VEGF and Angiopoietin-1 (Ang-1) protein expression. Therefore our results demonstrated for the first time that sildenafil is a very potent pro-angiogenic factor.

Expert Rev Cardiovasc Ther 2006 May; 4(3): 361-74 (Read article online)

Tulloh R

Idiopathic pulmonary arterial hypertension is a rare and potentially fatal condition. Without treatment, survival is only approximately 2.8 years from diagnosis. However, if the pulmonary hypertension is secondary to other causes, especially to congenital heart disease, it is possible to survive for 30 years or more without treatment. In recent years, remarkable progress has been made, risk factors have been identified and improved imaging techniques, including echocardiography, computer tomography and magnetic resonance imaging, are available. The condition can affect children at any age from fetal life through to adulthood. Patients can present to the respiratory pediatrician with unresponsive asthma, to the neurologist with faints or to the general pediatrician with failure to thrive. Over the last few years there have been significant developments in the available therapy for managing this complicated disease, which have improved the prognostic outlook, such as oral bosentan and sildenafil, intravenous epoprostenol and interventional catheterization with atrial septostomy. This article reviews the current knowledge about causation, investigation and treatment of children with pulmonary hypertension in the clinical setting.

Expert Rev Cardiovasc Ther 2006 May; 4(3): 293-300 (Read article online)

Hemnes AR, Champion HC

Pulmonary hypertension is a devastating disorder, characterized by vascular proliferation, intimal hypertrophy and vasoconstriction. In this disorder, alterations in the nitric oxide pathway have borne out to be important in not only vascular proliferation, but also in the maintenance of vascular tone. After synthesis by soluble guanylate cyclase, cGMP effects vasodilation via protein kinase G and other mediators, and is hydrolyzed by phosphodiesterases (PDEs). PDE5 is abundantly expressed in the mammalian lung and its inhibition by sildenafil has been demonstrated to improve pulmonary vascular physiology in vitro and in vivo animal models of pulmonary hypertension. Recent human data has confirmed the efficacy of sildenafil in therapy for humans with pulmonary arterial hypertension. The following review will discuss the underlying basic science supporting the use of sildenafil, as well as human evidence supporting the critical role of this drug in therapy of patients with pulmonary hypertension.

Actas Urol Esp 2006 Jan; 30(1): 67-79 (Read article online)

Rodríguez Vela L, Lledó García E, Rajmil O, Mo D, Cassinello A, Casariego J

OBJECTIVE: To compare patient preference for sildenafil citrate (sildenafil) vs. tadalafil and for their respective dosing instructions in a cohort of Spanish patients with erectile dysfunction (ED). MATERIAL AND METHODS: Sixty four Spanish patients from a multicenter, two period, cross-over, double-blind study (265 patients enrolled in total) were randomized to receive on-demand sildenafil 50 mg or tadalafil 20 mg for 12 weeks and afterwards were crossed over to the alternate regimen for another 12 weeks to assess drug preference in an extension period of the study. Similarly, to evaluate preference for their respective dosing instructions, 30 patients were randomized to one of the 2 arms treated with tadalafil: one with sildenafil (S) dosing instructions and the other with tadalafil (T) dosing instructions. RESULTS: Seventy percent of 56 patients completing the study chose to receive tadalafil treatment versus sildenafil treatment (30%) in the extension period (p<0.01). Correspondingly, 73% of 13 evaluating each drug dosing instructions preferred T dosing instructions (p>0.05). Preference did not vary with age, concomitant diseases and previous use of sildenafil. CONCLUSIONS: In this study, 7 out of 10 patients preferred tadalafil and its dosing instructions to sildenafil, for the treatment of their ED.

Rev Neurol (Paris) 2006 May; 162(5): 651-652 (Read article online)

Koussa S, Hage Chahine S, Tohmé A, Riachi M

EPILEPTIC SEIZURES AND VARDENAFIL.: Introduction. Epileptic seizures complicating treatment with selective inhibitors of phosphodiesterase type 5 are scarcely reported. Case report. A previously non-epileptic 78-year-old patient presented with a partial epileptic seizure following oral intake, for the second time, of 10mg of vardenafil (Levitra(R)). The brain MRI failed to show any preexisting lesion. To our knowledge, only 2 cases of generalized tonic-clonic seizures induced by sildenafil (Viagra(R)) use have been reported. In our patient, the seizure could be due to the epileptogenic potential of the drug or to its vascular complications. CONCLUSION: Further studies are needed to elucidate the association of phosphodiesterase inhibitors use and epileptic seizures.

Med Mycol 2006 May; 44(3): 253-9 (Read article online)

Weinberger M, Mahrshak I, Keller N, Goldscmied-Reuven A, Amariglio N, Kramer M, Tobar A, Samra Z, Pitlik SD, Rinaldi MG, Thompson E, Sutton D

We report a case of endogenous endophthalmitis due to a sporodochial-forming species of Phialemonium curvatum. The infection led to the enucleation of the affected eye, but there was no evidence of systemic dissemination. The isolated P. curvatum produced aggregates of phialides, many occurring on coils or in verticils, which eventually develop into sporodochia. The initial and post-enucleation isolates revealed they were identical to strains of P. curvatum from Israel causing disseminated disease in patients practicing intracavernous autoinjections for the treatment of erectile dysfunction. The reported case had unusual clinical and microbiological features. Despite the route of acquisition and the lack of systemic antifungal therapy, the infection did not spread beyond the eye. The morphology of the phialides aggregates was also unique, and the distinction between Volutella and Acremonium is discussed. This case expands the spectrum of infections due to Phialemonium species, and reveals a novel way of developing fungal endophthalmitis.

Med Hypotheses 2006 May 13; (Read article online)

Simpson JD, Doux JD, Lee PY, Yun AJ

Peripheral arterial disease in the legs represents a subset of atherosclerosis that manifests a particularly sinister profile. A predominance of sympathetic activity in the periphery favors the development of neurogenic atherosclerosis. Atherosclerosis may then produce flow derangements and decreased physical activity that serves to escalate sympathetic bias in a vicious cycle. Restoration of normal flow in peripheral arterial disease may not only produce local benefit due to improved perfusion, but also represent a gateway to correcting many systemic conditions that may at first glance appear unrelated but share a common etiology of autonomic dysfunction, such as gout, acute coronary syndromes, stroke, sleep apnea, arrhythmias, depression, erectile dysfunction, inflammation, hypercoagulability, sleep disorders, bowel dysfunction, renal failure, and aging.

Curr Med Res Opin 2006 May; 22(5): 939-948 (Read article online)

Steidle CP, Stecher VJ, Pace C, Tseng LJ,

BACKGROUND: The quality of life consequences of erectile dysfunction (ED) include depression, anxiety, and loss of self-esteem. The Self-Esteem And Relationship (SEAR) questionnaire is a validated, patient-administered, psychometric instrument specific to ED.OBJECTIVE: To determine correlations between erectile function (EF), intercourse success, and emotional well-being measured with the SEAR questionnaire in men treated with sildenafil citrate for ED and stratified by age (< 50 years, 50-65 years, and > 65 years).Research design and methods: This was an open-label, flexible-dose trial of sildenafil (25, 50 and 100 mg) administered for 10 weeks to 382 men with ED (mean +/- SD age, 55 +/- 13 years; mean ED duration, 4 years), which was conducted at 62 centers in the United States.MAIN OUTCOME MEASURES: Analysis (by intent-to-treat, n = 368) of the change from baseline to the week-10 endpoint in the SEAR questionnaire Self-Esteem subscale, the intercourse success rate (percent of occasions at which an erection that lasted long enough for successful intercourse was achieved), and their correlation.RESULTS: For the overall population, there was mean +/- SD improvement (p < 0.0001, paired t-tests) in the Self-Esteem subscale (56 +/- 25 to 79 +/- 22) and intercourse success rate (21 +/- 30% to 70 +/- 36%), which showed positive correlation (p < 0.0001). Secondary outcomes (i.e., EF domain of the International Index of Erectile Function; event log frequency of erection hard enough for sexual intercourse and of ejaculation/orgasm) also improved (p < 0.0001) and correlated positively with the SEAR Self-Esteem subscale and Sexual Relationship domain (p < 0.05 for all correlations). All 10 correlations were positive (p < 0.05) in men aged 50 to 65 years, eight were positive in men aged > 65 years, and six were positive in men aged < 50 years. The most common treatment-related adverse events were mild-to-moderate headache (12% of patients), vasodilatation (7%), and rhinitis (4%).CONCLUSIONS: Men treated with sildenafil for ED demonstrated improved erectile function and an increased intercourse success rate, which correlated positively with improvement in SEAR measures of self-esteem and sexual relationship.

Pediatr Pulmonol 2006 May 15; (Read article online)

Katz SL, Adatia I, Louca E, Leung K, Humpl T, Reyes JT, Coates AL

OBJECTIVES: Sildenafil, tezosentan, and prostacyclin reduce pulmonary vascular pressures in pulmonary hypertension, but have potential to vasodilate the systemic circulation. Nebulized vasodilators allow targeted drug delivery, high local drug concentrations, less systemic hypotension, and better matching of the lung's ventilation and perfusion. We aimed to estimate pulmonary deposition of these drugs from commonly employed nebulizers using in vitro techniques and to create a mathematical model to predict inspired mass of aerosol. DESIGN: Lung deposition was estimated by characterization of drug output and particle size distribution (PSD) of nebulizers using helium-neon laser diffraction techniques. A mathematical model for each device was created to estimate pulmonary deposition using patients' breathing patterns and was verified with a mechanical-breathing model. RESULTS: Total output and PSD were similar for the Hudson Updraft II and Whisperjet nebulizers, consisting of half the nebulizer's charge, with (1/4) of particles

Expert Opin Ther Targets 2006 Jun; 10(3): 445-57 (Read article online)

Burnett AL, Musicki B, Jin L, Bivalacqua TJ

Oxidative and/or nitrosative stress is implicated in the pathogeneses of assorted penile disorders of clinical significance, notably erectile dysfunction, priapism and penile fibrosis. It is becoming increasingly recognised that the generation and activity of reactive oxygen and nitrogen species in the penis influence vascular homeostasis of this organ, with adverse effects exerted at cellular and molecular levels. Furthermore, these elements may interact with molecular signalling pathways operating in the penis, modulating their functional roles. This interaction in particular suggests that by accessing molecular targets associated with oxidative/nitrosative stress in the penis, new pharmacotherapeutic approaches may be developed to promote normal erectile ability and preserve erectile tissue health. This notion pertains to, but also extends beyond, interventions which predictably target components of the nitric oxide-based signal transduction pathway for the on-demand treatment of erectile dysfunction. The next line of pharmaceuticals for disorders of the penis, in general, may well spawn from an integrative understanding of the complex regulatory interactions influenced by, as well as influencing nitric oxide signalling in this organ.

Actas Urol Esp 2006 Feb; 30(2): 159-69 (Read article online)

Atienza Merino G

The erectile dysfunction is a pathology that, with different degrees of intensity, affects nearly the 20% of the spanish adult men. The treatment is usually performed in stages, reserving the penile prosthesis for when other previous treatments have failed. The aim of this work is to evaluate, according to the state of present knowledge, the effectiveness and security of the penile prosthesis for the treatment of the erectile dysfunction. With this purpose 52 articles were selected, observing a 5 years prosthesis survival of 78-91% and a 3-8% of surgical complications. Mechanical failures and infection percentages were smaller in the semi-rigid prosthesis that in the inflatable ones, with high levels of postoperative satisfaction in patients as well as in their couples, even greater than in other treatments available at the present time. The penile prosthesis implantation must be reserved for the organic erectile dysfunction when previous treatments have failed, evaluating the risk-benefit relation and informing the patient of the results that are hoped to be obtained and of the possible complications that can arise. In view of the great concern of our society with the erectile function and the availability of effective drugs, an increase in the demand of penile prosthesis implantation is predictable in those patients highly motivated, but refractory to the less invasive treatments.

Urol Nurs 2006 Apr; 26(2): 156-9 (Read article online)

Moyad MA, Merrick GS

Educating patients on the basic cardiovascular disease (CVD) risk markers such as cholesterol can be difficult in any medical setting, but especially in urology where patients are being evaluated for non-cardiovascular conditions. Primary reasons for discussing cholesterol or cardiac risk factors and assessment in urology include (a) the primary cause of death of men and women in the United States and most countries around the world is CVD; (b) the primary or secondary cause of death from the largest cancer prevention trials (high or average risk) is CVD; (c) the primary or secondary cause of death in men with prostate cancer is CVD; (d) there may be a correlation in some of the mechanisms that contribute to CVD and mechanisms that contribute to numerous urologic conditions, such as benign prostatic hyperplasia, bladder cancer, erectile dysfunction, female sexual dysfunction, kidney cancer, and prostate cancer; and (e) one of the better methods to monitor the success of lifestyle changes for the patient in urology is to monitor these CVD markers, as is the case in some lifestyle studies of men with prostate cancer.

Urology 2006 May; 67(5): 1043-8 (Read article online)

Burnett AL, Bivalacqua TJ, Champion HC, Musicki B

OBJECTIVES: Recurrent ischemic priapism describes a disorder of repeated episodes of prolonged penile erection that frequently leads to devastating complications of erectile tissue damage and erectile dysfunction. A mechanistic role for dysregulated phosphodiesterase 5 (PDE5) in the deranged smooth muscle response of the corpus cavernosum of the penis offers new understanding about the pathogenesis of the disorder and suggests that PDE5 may serve as a molecular target for its treatment and prevention. We explored the use of PDE5 inhibitors to treat recurrent priapism, based on the hypothesis that the erection regulatory function of PDE5 would be regularized by this treatment and protect against further episodes. METHODS: We administered PDE5 inhibitors using a long-term therapeutic regimen to 3 men with sickle cell disease-associated priapism recurrences and 1 man with idiopathic priapism recurrences. RESULTS: Long-term PDE5 inhibitor treatment alleviated priapism recurrences. CONCLUSIONS: These observations support the hypothesis that PDE5 dysregulation exerts a pathogenic role for priapism associated with hematologic dyscrasias, as well as idiopathic priapism. Although these preliminary findings suggest that continuous, long-term PDE5 inhibitor therapy may be useful as a preventative strategy for priapism, additional evaluation in the form of a controlled clinical trial is needed.

BJU Int 2006 Jun; 97(6): 1242-6 (Read article online)

Nickel JC, Elhilali M, Emberton M, Vallancien G,

OBJECTIVE To determine the efficacy and safety of the selective alpha(1)-blocker alfuzosin in men with lower urinary tract symptoms (LUTS) and painful ejaculation, compared with those with LUTS only, as painful ejaculation is one of the most prevalent, differentiating and bothersome symptoms in men with chronic prostatitis/chronic pelvic pain syndrome. PATIENTS AND METHODS In all, 4857 sexually active men with LUTS had an evaluable answer to the Danish Prostate Symptom Score for Sexual Symptoms question related to pain/discomfort on ejaculation at enrolment in a 6-month open-label study with alfuzosin 10 mg once daily. Efficacy was analysed at the endpoint in the intent-to-treat population. RESULTS Of the 4857 men, 997 (20.5%) had pain/discomfort on ejaculation and 889/997 (89.2%) considered it was a problem. At inclusion, men with painful ejaculation had more severe LUTS and bother than men with LUTS only. Erectile dysfunction (ED) and reduced ejaculation were more prevalent (74.5% and 71.9%, respectively) and bothersome in men with painful ejaculation than in those with no pain (59.6% and 57.4%, respectively). Under alfuzosin treatment, all variables in both groups significantly improved from baseline; men with painful ejaculation compared to LUTS-only had similar improvements in weighted scores for LUTS (-7.8 vs -7.7), bother (-1.7 vs -1.7), and reduced ejaculate (-0.5 vs -0.4) but greater improvements in ED (-0.6 vs -0.4; P < 0.001). The weighted score for painful ejaculation decreased from 2.2 to 0.8 (P < 0.001). Alfuzosin was well tolerated in both groups. CONCLUSIONS This 6-month open-label study suggests that alfuzosin 10 mg once daily significantly improves LUTS, quality of life and sexual function in men with prostatitis-like symptoms, and is well tolerated.

BJU Int 2006 Jun; 97(6): 1252-5 (Read article online)

Horváth K, Walter G, Varga A, Romics I

OBJECTIVE To assess the clinical efficacy and safety of the combined alpha(1)- and postsynaptic alpha(2)-blocker GYKI-16084 compared to placebo during a 28-day active treatment of patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS After a 28-day placebo run-in phase, 7.5 and 15 mg GYKI-16084 or placebo were administered twice daily for 28 days to patients with BPH in a randomized single-blind Phase II study. Efficacy was primarily determined by changes in the American Urological Association (AUA) symptom scores and maximum urinary flow (Q(max)), while safety was assessed by orthostatic changes and adverse-event profile. A simplified International Index of Erectile Function questionnaire was used to assess effects on erectile function. RESULTS Data from 63 patients were evaluated; the decrease in the AUA score during the active phase was greater in the 15 mg group (-6.05, -32.7%) than in the placebo (-4.3, 22.7%) or 7.5 mg (-3.55, -19.5%) groups. Q(max) improved in both active treatment groups (+3.3 and +2.16 mL for the 7.5 and 15 mg groups, respectively) compared to placebo (+1.29 mL). None of the drug-related adverse events associated with selective alpha(1)-blockers were reported. CONCLUSION The combined alpha(1)- and postsynaptically selective alpha(2)-blocker GYKI-16084 significantly improved the AUA symptom scores and increased Q(max) in patients with BPH, without inducing any adverse reaction, orthostatic changes or erectile dysfunction.

World J Urol 2006 Apr 11; (Read article online)

Ponholzer A, Brössner C, Struhal G, Marszalek M, Madersbacher S

The objective of this study was to assess lower urinary tract symptoms (LUTS), urinary incontinence (UI), erectile dysfunction (ED) and quality of life after radical prostatectomy (RPE) and external beam radiation therapy (EBRT) in a "real-life" setting. A consecutive series of patients undergoing routine follow-up after RPE and EBRT at 28 Austrian institutions were analyzed. Men who received adjuvant therapy were excluded. All patients completed a questionnaire on (a) LUTS and UI, (b) sexual function and (c) quality of life. A total of 364 patients following RPE and 82 after EBRT entered this study and were compared in a matched pair analysis (1:1) based on age, PSA at diagnosis and follow-up (RPE: n=82; EBRT: n=82). Mean time-interval between treatment and current investigation was 4.6 years for RPE and 4.4 years for EBRT (n.s.). UI was reported by 41.3% after RPE and 18.8% after EBRT (P=0.001). Urgency was more frequent after EBRT, this difference, however, did not reach statistical significance. Moderate to severe ED (IIEF-5, <17) was present in 80.0% after RPE and in 80.8% after EBRT (n.s.). On a ten-point scale, RPE-patients rated their quality of life higher (7.3) than after EBRT (6.7) (P=0.01). In this "real-life" setting, RPE and EBRT had significant, yet divergent effects on LUTS, UI and sexual function. The respective numbers were substantially higher than those usually reported by physician-directed studies and centers of excellence.

Urology 2006 May; 67(5): 1033-7 (Read article online)

Teloken PE, Smith EB, Lodowsky C, Freedom T, Mulhall JP

OBJECTIVES: To conduct a study using validated sexual function and sleepiness inventories to define whether sleep apnea syndrome (SAS) is associated with erectile dysfunction and whether any correlation exists between the severity of SAS and the severity of erectile dysfunction. Previous work has suggested that sleep disorders are associated with erectile dysfunction. METHODS: Men presenting to a sleep clinic with symptoms consistent with SAS were given the Epworth Sleepiness Scale and an erectile dysfunction risk factor inventory, the International Index of Erectile Function. A database was constructed and statistical analysis conducted to define the correlation between the two entities. RESULTS: A total of 50 men met the criteria for inclusion. Of the 50 men, 60% had abnormal Epworth Sleepiness Scale scores and 80% of these patients had erectile dysfunction as determined by inventory scores compared with 20% of the men with normal Epworth Sleepiness Scale scores. There were statistically significant differences between men with normal and abnormal sleepiness scores for the total and erectile function domain of the International Index of Erectile Function. The correlation between the severity of the sleepiness and the severity of erectile dysfunction was good (r = -0.80, P = 0.012). CONCLUSIONS: Men presenting with symptoms consistent with SAS have a significant risk of erectile dysfunction, and the correlation between the severity of sleep apnea and the severity of erectile dysfunction is strong.

J Perinatol 2006 May 4; (Read article online)

Lemus-Varela ML, Sola A, Gómez-Meda BC, Zamora-Perez AL, Ramos-Ibarra ML, Batista-González CM, Zúñiga-González GM

Objective:To determine sildenafil citrate (SC) genotoxicity and cytotoxicity in the Callithrix jacchus.Study design:Fifteen organisms were assigned to one of three groups as follows: experimental (25 mg/kg of SC); negative control (glucose solution 5%); and positive control (3 mg/kg of cytocine arabinoside). Systemic hemodynamic changes were monitored in each animal before and after each treatment. A drop of blood was obtained before and after the treatment at 24-120 h. Smears were made and the frequency of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes (PCE) was counted.Results:No significant differences in MNE, MNPCE and PCE were found in the group that received sildenafil and negative control. A significant increase in genotoxicity and cytotoxicity was observed in the positive control group. No changes were observed in systemic hemodynamic changes.Conclusion:The macro-dose of SC lacks genotoxic, cytotoxic or systemic hemodynamic changes effects in this species.Journal of Perinatology advance online publication, 4 May 2006; doi:10.1038/sj.jp.7211518.

J Urol 2006 Jun; 175(6): 2345-9 (Read article online)

Demir O, Murat N, Aslan G, Gidener S, Esen AA

PURPOSE: We investigated the relationship of adrenergic responses in corpus cavernosum tissues in the presence of BOO using the alpha1-adrenergic receptor antagonist doxazosin (Pfizer, New York, New York) and the rho-kinase inhibitor Y-27632 (Calbiochem, San Diego, California). MATERIALS AND METHODS: CCSM tissue was obtained from patients who underwent penile prosthesis implantation. Patients were divided into 2 groups according to the presence of BOO. The submaximal (EC(80)) concentration of phenylephrine (Sigma Chemical Co., St. Louis, Missouri) was calculated by evaluating adrenergic activity responses with cumulatively applied phenylephrine. After achieving a stable contraction plateau test compounds were put in an organ bath. The relaxant potencies of doxazosin and Y-27632 were expressed as the percent of inhibition of the contraction plateau induced EC(80) concentration of phenylephrine. Relaxation responses in the 2 groups were compared. RESULTS: At the highest dose of increasing concentrations phenylephrine generated 70% more contraction response in the BOO positive group than in the BOO negative group. Doxazosin and Y-27632 caused concentration dependent relaxation in CCSM precontracted by phenylephrine. With doxazosin significantly higher relaxation responses were attained in the BOO positive group in terms of log IC(50) and the maximal relaxation response (p = 0.0353 and 0.0003, respectively). Maximum relaxation responses following Y-27632 administration were significantly higher in the BOO positive group. CONCLUSIONS: The contractility of human corpus cavernosum is increased in the presence of BOO. Doxazosin and Y-27632 generate effective CCSM relaxation in the presence of BOO. Doxazosin and Y-27632 may be the alternatives for the treatment of erectile dysfunction associated with BPH.

J Urol 2006 Jun; 175(6): 2350-2353 (Read article online)

Orhan I, Onur R, Taşdemir C, Ayar A, Kadıoğlu A

PURPOSE: Sildenafil is reported to regulate smooth muscle contractility through nitric oxide-cyclic guanosine monophosphate, not only in the corpus cavernosum. Its possible effects on seminal vesicle contractility might be of importance with respect to premature ejaculation. We investigated the effects of sildenafil citrate (Pfizer, New York, New York) on agonist induced isometric contractions of the rat seminal vesicle in vitro. MATERIALS AND METHODS: Seminal vesicles isolated from adult male Wistar rats were suspended in an organ bath and contracted by NE (10 muM), ACh (10 muM) or KCl (60 mM) (Sigma, Deisenhofen, Germany). The effects of sildenafil citrate (100 to 300 muM) were evaluated in terms of mean contraction amplitude, the area under force-time curves and isometric contractility indexes. RESULTS: Sildenafil citrate (300 muM) significantly inhibited the mean amplitude +/- SEM of contractile responses induced by NE (1,061 +/- 153 vs 271 +/- 65 mg, p <0.0001), ACh (475 +/- 51 vs 68 +/- 17 mg, p <0.0001) and KCl (546 +/- 71 vs 59 +/- 18 mg, p <0.0002). It also caused dose dependent concomitant decreases in the area under force-time curves. Additionally, pretreatment with sildenafil citrate markedly prevented the contractile response to NE, ACh and KCl. CONCLUSIONS: Our results indicate that sildenafil citrate inhibits the contractions of isolated rat seminal vesicle that are induced by NE, ACh or KCl. Future studies may support an in vivo effect of sildenafil for delaying or inhibiting seminal vesicle emission, thereby, promoting improvement in patients with premature ejaculation.