A Public Health Communication Intervention Using Edutainment and Communication Technology to Promote Safer Sex among Heterosexual Men Patronizing Entertainment Establishments.

It is a challenge to reach out, develop and implement a communication intervention for heterosexual men (HSM) patronizing entertainment establishments (EEs) to promote safer sex. We described the theoretical basis and process from assessment to implementation where edutainment (talk shows) and communication technology (interactive web portal) was implemented. A female comedian hosted the talk shows. The portal contained an HIV risk profile calculator with individually tailored strategies to lower risk; two videos on real-life stories of unsafe sex and exit strategies to avoid casual or paid sex; as well as online support. We integrated edutainment, social cognitive theory (SCT) and the elaboration likelihood model (ELM). Edutainment techniques like humor through jokes, fun through games, and narrative persuasion through real-life accounts were applied. The SCT focused on modifying attitudes and social norm on sexual well-being, increasing self-perceived HIV/STI risk as well as building self-efficacy and skills in condom use. We applied the ELM to guide communication strategies and message development. For peripheral processing, we used cues like comedian delivery and charisma. For central processing, we focused on argument framing, issue involvement, argument quality, and modeling. The intervention was effective in promoting condom use with casual partners among the target group in Singapore.

Role of the serotonergic pathway in uterotonic activity of Ananas comosus (L.) Merr. - An in vitro and in vivo study.

BACKGROUND: Ananas comosus (L.) Merr. has been used as a traditional medicine in inducing abortion in many countries. Our previous in vitro experiments showed that the aqueous fraction (F4) of A. comosus extract stimulated the rat and human uterine contractions. PURPOSE: The aim of this study was to identify the bioactive compound and further investigate the molecular mechanism of F4 induced contraction and the in vivo uterotonic effect of F4. MATERIALS AND METHODS: Organ bath studies were employed to compare the stimulatory effect of F4 in non and late pregnant uterine tissue followed by isolation of protein from late pregnant uterine tissue for the western blot analysis. The PhysioTel transmitter was implanted in pregnant SD rats to measure the changes in intrauterine pressure (IUP). Analyses of the crude extract and active principle in F4 was performed using LC-HRMS. RESULTS: Ripe F4 in a similar manner as serotonin produced a greater stimulatory response in late pregnant than non-pregnant uterine tissue without significant change in potency; ripe F4 also increased ERK phosphorylation which eventually led to a significant increase of the final product, MMP-13. In pregnant rats (E18), oral ripe F4 (1.5 g.100 g-1 body weight) and ergometrine (1 mg) did not stimulate the uterine contraction probably due to the low level of estradiol and as a consequence low 5-HT receptors at the time of administration. In contrast, in postpartum rats, oral administration of F4 and ergometrine produced a significant increase in maximal IUP to 4.3 and 4.9 folds of basal IUP respectively. Contrary to the folklore use, unripe F4 did not stimulate the uterine activity during pregnancy and postpartum. Bioassay guided fractionation identified serotonin as a major bioactive compound in ripe F4. CONCLUSIONS: Our data clearly indicate that the uterotonic effect of ripe F4 is mediated via the serotonergic pathway and suggest that serotonin rich diet may increase the peripheral serotonin and implicate in diverse physiological functions, including uterine motility.

Potent tocolytic activity of ethyl acetate fraction of Ananas comosus on rat and human uteri.

The aim of this study was to investigate the tocolytic properties of Ananas comosus extract in rat and human uterine tissue in vitro and in the rat in vivo. Organ bath technique was employed to perform functional studies in vitro. The PhysioTel transmitter was implanted in SD rats to measure the changes in intrauterine pressure (IUP) in vivo. Analyses of F2 was performed using LC-HRMS. F2 produced a non-selective inhibitory response on oxytocin, prostaglandin F2α, acetylcholine and KCl. The inhibitory activity of F2 on oxytocin-induced contraction was not attenuated by propranolol, TEA, glibenclamide and indomethacin. Nω-Nitro-L-arginine, a nitric oxide synthase inhibitor, suppressed the maximal tocolytic activity of F2 by 25%. DIDS, an inhibitor of chloride channels, appeared to suppress the relaxant effect of F2. F2 suppressed the oxytocin-induced contraction in Ca2+ free solution. The in vivo tocolytic activity of F2 and ritodrine were observed in non-pregnant rats during the estrous stage by suppressing the frequency and amplitude of IUP peaks following intrauterine administration. Chemical analysis confirmed the involvement of citric acid in the tocolytic activity of F2. However, another less polar fraction is essential to accompany citric acid to produce such potent inhibitory response of F2. It is likely that F2 exerted tocolytic activity by multiple mechanisms, including antagonizing L-type Ca2+ channels, interfering with the intracellular Ca2+ release mechanism and releasing nitric oxide. F2 would be a promising candidate to develop as a tocolytic agent.

Use of single-question screening for erectile dysfunction: a study of at-risk Asian men in primary health care.

This study assesses the validity of a single-question screener for erectile dysfunction (ED) in men at risk in comparison to a standard validated tool - the five-item version of the International Index of Erectile Function (IIEF-5). A total of 174 men with at least one risk factor for ED were studied, with 58.0% and 10.9% of the study respondents meeting the criteria for their erectile impairment by IIEF-5 and single-question screener respectively. Our results suggest that in spite of high feasibility, a simplified, single-question screener has low sensitivity in capturing ED prevalence, even in an at-risk population, within the Asian context.

Endothelial colony forming cells from human umbilical cord blood improved severe erectile dysfunction in obese type II diabetic rats.

AIM: To investigate the effect of intracavernous injection of human umbilical cord blood derived endothelial colony forming cells (HUCB ECFCs) on erectile dysfunction (ED) in Zucker Diabetic Fatty (ZDF) rat model. METHODS: Erectile function was assessed by cavernous nerve electrostimulation in ZDF rats aged 20-28 weeks. Following confirmation of severe ED at the age of 28 weeks, 21 ZDF rats were randomly assigned to three experimental groups: 1 million ECFCs, 2 million ECFCs, and phosphate buffered saline (PBS). Four weeks after intracavernous injection, the efficacy of ECFCs was quantified by intracavernous pressure (ICP) measurement, Masson's trichrome staining, immunohistologic and immunoblot analyses and TUNEL assay. KEY FINDINGS: Intracavernous ECFC administration improved ICP in a dose-dependent manner in comparison to the age-matched PBS group. Functional improvement in ICP was accompanied by a significant restoration of the cavernosal endothelial and smooth muscle cell content and cavernosal nerve function. The percentage eNOS and nNOS positive cavernosal cells, and their respective protein expression levels and nNOS positive cells in the dorsal penile nerve in 2 million ECFCs treated groups were significantly higher than the PBS group. TUNEL stain quantification showed a significant decrease in cavernosal apoptosis following ECFC treatment. SIGNIFICANCE: The results are expected to provide a scientific basis to further study the clinical application of HUCB ECFCs in ameliorating ED in human. CONCLUSIONS: HUCB ECFCs significantly improved severe ED in ZDF rats through improvement of the nerve and endothelium function and restoration of smooth muscle in the cavernosum by overcoming the cavernosal apoptosis.

Efficacy of Human Immunodeficiency Virus/Sexually Transmitted Infection Trial on Condom Use Among Heterosexual Men Patronizing Entertainment Establishments Who Engaged in Casual or Paid Sex in Singapore.

BACKGROUND: We assessed the efficacy of a multi-component sexual health promotion program on condom use and human immunodeficiency virus (HIV)/sexually transmitted infection (STI) testing among heterosexual men (HSM) patronizing entertainment establishments who engaged in casual or paid sex in Singapore. METHODS: This was a quasi-experimental trial with a comparison group using cross-sectional surveys at baseline and 6 months postintervention. A locality patronized by local HSM was assigned the intervention, a comparable and distant area served as the comparison site. Using time location sampling, cross-sectional samples of these men were assessed on sexual behaviors using an anonymous questionnaire at baseline (n = 604) and 6 months postintervention (n = 360) in both groups. The coprimary outcomes were condom use at last vaginal and oral sex with casual partner respectively. Mixed effects Poisson regression model accounting for clustering by establishment was used to compute the adjusted prevalence ratio (aPR) of the outcomes postintervention. RESULTS: At postintervention, the intervention group was more likely than the comparison group to report condom use at last vaginal (aPR, 1.41; 95% confidence interval [CI], 1.05-1.89) and oral (aPR, 1.70; 95% CI. 1.11-2.61) sex, respectively, with casual partner. Similar findings were found for consistent condom use in the last 6 months for vaginal (aPR, 1.67; 95% CI, 1.13-2.48) and oral (aPR, 1.97; 95% CI, 1.16-3.32) sex, respectively, with casual partner. The HIV/STI testing was not significantly higher in the intervention than the comparison group (aPR, 1.43; 95% CI, 0.98-2.09). CONCLUSIONS: This trial was effective in promoting condom use with casual partners but not HIV/STI testing among HSM in Singapore.

Investigation of uterotonic properties of Ananas comosus extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: In folklore medicine Ananas comosus (pineapple) is reputed to act as an abortifacient and in expectant women as a means of inducing labor. Several reports have claimed abortifacient property of A. comosus fruit (ripe or unripe). Ripe fruit has been used orally as traditional medicine in inducing abortion in Kerala state of India while the juice of unripe fruit was used for abortion in Bangladesh. However, scientific evidence supporting the efficacy of pineapple extracts in inducing uterine contractions is clearly lacking. AIM OF THE STUDY: This study investigated the pharmacological effects of different fractions of pineapple extract with a range of maturities to identify the most potent uterotonic fraction. MATERIALS AND METHODS: The ethanolic crude extracts of pineapple (edible part) were prepared and fractionated through a series of liquid-liquid partitions. Fractions were separately tested on isolated uterine muscle from pregnant SD rats and human pregnant myometrium, which were cut into strips along the longitudinal axis of uterus. The strips were mounted vertically in organ baths (37°C) and exposed to cumulative addition of fractions (0.1-10mgml-1), serotonin (0.05-5µM) and different inhibitors to delineate the mechanism of action of the active ingredients of the extract. RESULTS: Aqueous fraction (F4) possesses uterine stimulant property which was blocked by verapamil but unaffected by indomethacin, prazosin and atosiban. Notably, ketanserin (10µM) diminished the maximal contractile response induced by both F4 and 5HT by 74.3% and 92.1% respectively. CONCLUSIONS: These results may indicate the presence of 5HT or 5HT-like compound(s) and serotonergic pathways may contribute to the uterotonic activity of pineapple extract.

An Update of the International Society of Sexual Medicine's Guidelines for the Diagnosis and Treatment of Premature Ejaculation (PE).

INTRODUCTION: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts. AIM: The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. METHOD: A comprehensive literature review was performed. RESULTS: This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years. Althof SE, McMahon CG, Waldinger MD, Serefoglu EC, Shindel AW, Adaikan PG, Becher E, Dean J, Giuliano F, Hellstrom WJG, Giraldi A, Glina S, Incrocci L, Jannini E, McCabe M, Parish S, Rowland D, Segraves RT, Sharlip I, and Torres LO. An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE). Sex Med 2014;2:60-90.

An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE).

INTRODUCTION: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts. AIM: The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. METHOD: A comprehensive literature review was performed. RESULTS: This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years.

Endogenous hydrogen sulfide insufficiency as a predictor of sexual dysfunction in aging rats.

OBJECTIVE: Our earlier studies showed that endogenous hydrogen sulfide (H(2)S) pathway contributed significantly to erectile function. In this study, we tested the hypothesis that age-dependent changes in the bioavailability of H(2)S increased the risk of erectile dysfunction (ED). METHODS: Young, adult (3-month) and older (18-month) male Sprague-Dawley rats (n = 6-8/group) were treated daily with sodium hydrosulfide hydrate (NaHS), DL-propargylglycine, sildenafil or l-NAME for 10 weeks. Subsequent to cavernous nerve electrical stimulation, intracavernosal pressure (ICP) responses were determined, and the samples were collected and processed for hormonal (plasma) and gaseous parameters (plasma and erectile corpus cavernosum [CC]) using standard assay protocols. RESULTS: Aging significantly reduced the ICP response (35.9 ± 2.0 mmHg vs. 45.2 ± 1.9 mmHg in young controls), which was countered by NaHS (53.5 ± 6.0) or sildenafil (52.8 ± 9.8) treatment. In these rats, marked increments to testosterone (T) or estradiol resulted from NaHS supplementation. Similar to age-dependent decline in NO, the plasma and CC level of H(2)S was significantly lower in senescent rats when compared with young animals (p < 0.05). CONCLUSION: Our results confirm that ED with aging may be linked to a derangement in the H(2)S pathway accompanied by low T levels. It is likely that a pharmacologic intervention delivering H(2)S will provide additional benefits to sexual function from an improved T milieu.

Characterizing behavior of corpus cavernosum in chloride-free condition.

OBJECTIVE: To elucidate the role of chloride currents in erectile function through characterizing the behavior of corpus cavernosum (CC) in chloride-free (Cf) medium, which has not been evaluated before. METHODS: Isolated rabbit CC strips were suspended in thermo-regulated organ baths containing oxygenated Tyrode for isometric tension recording. Cf Tyrode was prepared by substituting sodium chloride, calcium chloride, and potassium chloride (KCl) with equivalent molar concentrations of sodium acetate, calcium acetate, and potassium acetate salts. Resting cavernosal tone and contractions by noradrenaline, histamine, and KCl were assessed in Cf Tyrode with or without chloride channel blockers, niflumic acid (NFA), and anthracene-9-carboxylic acid (A9C). RESULTS: Withdrawal of extracellular chloride caused myogenic contractions in the unstimulated CC strips (n = 18). In addition, peak contractions by noradrenaline (n = 14) and histamine (n = 13) were augmented in Cf buffer by 47.2 ± 5.9% and 85.4 ± 13.2%, respectively (P <.05), whereas KCl contractions were not significantly altered (17.6 ± 4.6%; n = 7). Interestingly, Cf buffer exerted opposing effects, potentiation and reduction, respectively, on the plateau phase of contractions mediated by noradrenaline and histamine. The stimulatory effect of Cf buffer on the intrinsic myogenic tone was diminished by NFA (30 µM), and A9C (300 µM-1 mM). NFA (30-100 µM), however, specifically reduced the plateau phase without significantly modifying the peak contraction of noradrenaline in Cf buffer. CONCLUSIONS: These results reiterate the importance of chloride currents as a mechanism underlying the maintenance of penile cavernosal tone. Thus, chloride channel could be an effective alternative target to regulate penile erection.

Effects of hydrogen sulfide on erectile function and its possible mechanism(s) of action.

INTRODUCTION: The current pharmacotherapy for erectile dysfunction (ED) relies significantly on the use of phosphodiesterase type 5 (PDE5) inhibitors, but quite a proportion of ED patients are resistant to this therapy, necessitating a search for an alternative treatment. We reviewed available published data to analyze current evidence of hydrogen sulfide (H(2) S) as a novel pharmacotherapeutic agent with supportive role in sexual function. AIM: To discuss the role of H(2) S in erectile function, its possible mechanism of action, and how this knowledge may be exploited for therapeutic use. METHODS: Pubmed and Medline search was conducted to identify original articles and reviews. MAIN OUTCOME MEASURES: Data from peer-reviewed publications. RESULTS: Animal studies using different species, including in vitro study done in humans, show evidence of H(2) S's pro-erectile effects. The mechanism behind is still unclear, but evidence in literature points out the involvement of K(+) (ATP) channel, modulation of protein with anti-erectile effects, as well as involvement of the nitrergic pathway through a complex cross-talk. A new drug called H(2) S-donating sildenafil (ACS6), which incorporated an H(2) S-donating moiety in sildenafil, has been developed. While more studies are still needed, this heralded a new pharmacotherapeutical approach, which is multipronged in nature. CONCLUSIONS: Given the mounting evidence of H(2) S's role in erectile function and how it appears to achieve its pro-erectile effects through different mechanisms, H(2) S represents a potentially important treatment alternative or adjunct to PDE5 inhibitors.

Endocrine milieu and erectile dysfunction: is oestradiol-testosterone imbalance, a risk factor in the elderly?

Oestrogens are not exclusive to the female gender but occur in moderate circulating levels of 25-70 pg ml⁻¹ in men, compared to 44-153 pg ml⁻¹ in women. Arising from aromatisation of testosterone (T), oestrogen is considered to have many opposing physiological functions and the progressive T decline in the aging male is associated with relative and/or absolute increase in serum oestradiol (E2). Sexual disinterest and erectile dysfunction (ED) in the elderly may well be due to pathophysiological E2-T imbalance; the altered hormonal ratio may also explain the higher incidence of ED in hyperestrogenism or following exposure to environmental/plant oestrogens.

Efficacy of red clover isoflavones in the menopausal rabbit model.

OBJECTIVE: To evaluate the effectiveness of phytoestrogens as alternatives for selective dysfunctional changes in the menopausal rabbit model. DESIGN: Prospective, vehicle-controlled experimental study. SETTING: Reproductive pharmacology laboratory in a university department. ANIMAL(S): Twenty-four rabbits with experimentally induced menopause and six intact controls. INTERVENTION(S): Surgical menopause was induced in 24 rabbits by ovariectomy. After 4 weeks of convalescence, three groups (n = 6) were given 100 microg/kg E(2) valerate, 100 microg/kg daidzein, or 6.68 mg/kg red clover extract daily for 12 weeks. The remaining six rabbits served as the operated control group. MAIN OUTCOME MEASURE(S): Vaginal blood flow using Doppler flowmetry, before, during, and after pelvic nerve stimulation; and measured parameters of uterine weight, femoral bone density, clitoral cavernosal histology, and hormone levels. RESULT(S): After pelvic nerve stimulation, blood flow increased remarkably in the daidzein-treated group. Serum E(2) and uterine weight increased significantly in the estrogen group. Cavernosal structure was well preserved in all three treatment groups, and bone mineral density was lowest in ovariectomized controls (0.3467 g/cm(2)) and highest in the red clover (0.4012 g/cm(2)) groups. CONCLUSION(S): Supplementing isoflavones for menopause leads to significant improvements in bone density, tissue integrity, and vaginal blood flow with minimal effect on uterine weight and may therefore be a viable alternative to conventional regimens using synthetic estrogens.

Role of chloride channels in the regulation of corpus cavernosum tone: a potential therapeutic target for erectile dysfunction.

INTRODUCTION: Recent electrophysiological recordings have identified the existence of outward, excitatory chloride (Cl(-)) currents in rat, rabbit, and human corpus cavernosum (CC) muscle cells. AIM: The aim of this study was to investigate the physiological role of Cl(-) currents in the maintenance of cavernosal muscle tone in isolated rabbit CC tissues. METHODS: CC strips (1 x 1 x 5 mm) were suspended in tissue bath chambers for isometric tension experiments. Spontaneous cavernosal tone and contractions elicited by field stimulation or administration of established smooth muscle constrictors were examined in the presence of chloride channel (ClC) blockers, niflumic acid (NFA), and anthracene-9-carboxylic acid (A9C). MAIN OUTCOME MEASURE: Both spontaneous myogenic activity and contractile responses to field stimulation, norepinephrine, histamine, and endothelin-1 were reduced by ClC blockers. Results. In CC strips exhibiting intrinsic myogenic tone, NFA (30 and 100 microM) and A9C (1 mM) caused a relaxation of the tone. In addition, spontaneous contractile activity in CC was abolished in the presence of either ClC blocker. In CC strips precontracted with norepinephrine, histamine, and endothelin-1, both ClC blockers significantly reversed the tone. The ability of NFA and A9C to reverse norepinephrine-induced tone was unaffected by N(omega)-nitro-L-arginine, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2-amine. In addition, neither indomethacin nor tetraethylammonium affected the relaxant response of NFA. NFA and A9C inhibited the neurogenic and norepinephrine-induced contractions in a concentration-dependent manner. While NFA exerted persistent inhibition on neurogenic contraction, inhibition of neurogenic contractions by A9C was readily reversible. On K(+)-depolarized CC, NFA induced a concentration-related relaxation, whereas A9C was inert, suggesting an additional mechanism of NFA on voltage-gated calcium channels. CONCLUSIONS: These results underline the importance of Cl(-) currents as a mechanism in the maintenance of cavernosal tone produced by adrenergic and various endogenous constrictors. Thus, the modulation of Cl(-) current, as an attractive and effective approach to regulate penile erection, and specific ClC blockers, as potential erectogenic agents, merits further research.

Hydrogen sulphide: a novel endogenous gasotransmitter facilitates erectile function.

INTRODUCTION: In a pilot study, we found that the novel gasotransmitter, hydrogen sulfide (H2S), had a vasodilatory and proerectile action on the cavernosum. In the present work, we explored the ability of the cavernosum to synthesize H2S and its mechanism on the cavernosal pathways. AIM: To evaluate the physiopharmacological responses and mechanism in the erectile function of H2S in rabbit cavernosum. METHODS: Rabbit corpus cavernosum (CC) smooth muscle tissue (N = 5) was homogenized and incubated with L-cysteine (10 mM) and pyridoxal 5'-phosphate (2 mM) to detect H2S formation. In isometric tension studies on rabbits (N = 12), the effect of sodium hydrogen sulfide (NaHS; stable H2S donor, 100 microM-3.2 mM) was evaluated on the relaxant and contractile pathways in the cavernous smooth muscle using standard pharmacological tools. MAIN OUTCOME MEASURES: In vitro evidences for cavernosal H2S formation and proerectile pharmacological effects. RESULTS: H2S was readily synthesized in the rabbit CC (2.1 +/- 0.4 nmol/mg protein). In organ bath studies, NaHS consistently relaxed the rabbit CC in a concentration-dependent manner. MDL 12,330A and 1-H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one inhibited the NaHS relaxation by 22.5% and 14.7%, respectively. All three enzyme inhibitors (aminooxyacetic acid [AOAA], beta-cyanoalanine [beta-CA], and DL-propargylglycine [PAG][1 mM]) markedly increased the noradrenergic contractile neurotransmission of CC strips to field stimulation with minimal reversal by cysteine (1 mM) indicating the possible inherent inhibition of the relaxant H2S formation. AOAA, beta-CA, or PAG had no significant effect on nitrergic relaxation of noradrenaline-precontracted CC strips. CONCLUSION: These pioneering studies provide evidence for the endogenous formation of H2S and its proerectile relaxant effect on the cavernosum, with the possibility of involvement of the cyclic adenosine monophosphate pathway.