Recent studies have revealed a significant relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), both of which commonly affect middle-aged and older men. These conditions share underlying causes, particularly endothelial dysfunction, atherosclerosis, and chronic pelvic ischemia (CPI). This study investigated the therapeutic potential of LDD175, a large-conductance Ca 2+ -activated K + channel (BKCa channel) opener, in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats. Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet. We assessed erectile and voiding functions by measuring intracavernosal pressure (ICP) and intraurethral pressure (IUP), respectively, after nerve stimulation. We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms. This study evaluated the effectiveness of LDD175 compared to standard treatments, such as sildenafil for ED and tamsulosin for LUTS. Therefore, the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP. Analysis revealed elevated levels of hypoxia-inducible factor-1α, transforming growth factor-β1 and β2 in cavernous tissue, and increased α1A-adrenoceptor expression in prostate tissue. LDD175 administration showed promising results, with dose-dependent improvements in ICP and IUP, and therapeutic effects comparable to those of established treatments. Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS, opening new possibilities for clinical application in the treatment of these interconnected conditions.
Male ; Animals ; Erectile Dysfunction/etiology* ; Rats, Sprague-Dawley ; Lower Urinary Tract Symptoms/etiology* ; Ischemia/drug therapy* ; Rats ; Tamsulosin ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects* ; Sildenafil Citrate/therapeutic use* ; Penis/blood supply* ; Disease Models, Animal ; Transforming Growth Factor beta1/metabolism* ; Pelvis/blood supply* ; Prostate/metabolism* ; Sulfonamides/therapeutic use* ; Large-Conductance Calcium-Activated Potassium Channels/agonists*

OBJECTIVE: To explore the effects of Qiwei No.3 combined with sildenafil on Rho kinase activity and AKT/eNOS pathways in the penile cavernous tissue of male rats with diabetic erectile dysfunction (DED). METHODS: We constructed a model of DED in 24 SD male rats by intraperitoneal injection of streptozotocin solution and injecting apomorphine into the neck after 8 weeks of feeding, equally randomized the model rats into a model control (MC), a sildenafil (S), a low-dose Qiwei No.3 combined with sildenafil (LQ+S) and a high-dose Qiwei No.3 combined with sildenafil (HQ+S) group, and took another 6 normal male rats as blank controls (BC). We treated intragastrically the animals in the BC and MC groups with normal saline, and those in the S, LQ+S and HQ+S groups with sildenafil (5 mg/kg/d), Qiwei No.3 (10 g/kg/d) + sildenafil (5mg/kg/d), and Qiwei No.3 (20g/kg/d) + sildenafil (5mg/kg/d), respectively. After 6 weeks of treatment, we recorded the number of penile erections of all the rats by injecting apomorphine into the neck, and measured the activity of Rho kinase and expressions of p-AKT and eNOS proteins in the corpus cavernosum by Western blot. RESULTS: Compared with the blank controls, all the DED model rats showed evidently elevated blood glucose and reduced body weight. The number of penile erections was significantly increased in the S, LQ+S and HQ+S groups in comparison with that in the model controls (P< 0.05), even higher in the HQ+S than in the S group (P< 0.05). The activity of Rho kinase in the penile cavernosum was significantly higher in the MC than in the BC group (P<0.05), but lower in the HQ+S than in the S group (P< 0.05). No statistically significant difference was observed in the expression level of the p-AKT protein in the penile cavernosum among the five groups of rats (P > 0.05). The expression of eNOS was remarkably up-regulated in the BC and HQ+S groups (P< 0.05) compared with that in the MC group, even more significantly in the HQ+S than in the LQ+S and S groups (P< 0.05). CONCLUSION The combination of high-dose "Qiwei No. 3" and sildenafil can improve erectile function in DED rats, which may be attributed to its effect of releasing more nitric oxide (NO) by inhibiting the activity of Rho kinase and up-regulating the expression of the e-NOS protein.
Animals ; Male ; Sildenafil Citrate ; Rats ; rho-Associated Kinases/antagonists & inhibitors* ; Rats, Sprague-Dawley ; Penis/drug effects* ; Erectile Dysfunction/etiology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Nitric Oxide Synthase Type III/metabolism* ; Diabetes Mellitus, Experimental/complications* ; Drugs, Chinese Herbal/therapeutic use*

Erectile dysfunction (ED) associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase (PK) has the potential to improve the erectile function of ED patients. This study aims to investigate the effect of PK on erectile function in streptozotocin-induced type 2 diabetic ED rats. To achieve this goal, we divided male Sprague-Dawley rats into five groups. One group was not treated, and the other four groups were treated with saline, sildenafil, PK or sildenafil, and PK, respectively, for 4 weeks after the induction of type 2 diabetic ED. Then, intracavernous pressure under cavernous nerve stimulation was measured, and penile tissue was collected for further study. Endothelial nitric oxide synthase levels, smooth muscle content, endothelium content, cyclic guanosine monophosphate (cGMP) levels in the corpus cavernosum, and neuronal nitric oxide synthase levels in the dorsal penile nerve were measured. Improved erectile function and endothelium and smooth muscle content in the corpus cavernosum were observed in diabetic ED rats. When treating diabetic ED rats with PK and sildenafil at the same time, a better therapeutic effect was achieved. These data demonstrate that intraperitoneal injection of PK can improve erectile function in a rat model of type 2 diabetic ED. With further research on specific mechanisms of erectile function improvement, PK may become a novel treatment for diabetic ED.
Animals ; Cyclic GMP/metabolism* ; Diabetes Mellitus, Experimental/physiopathology* ; Erectile Dysfunction/physiopathology* ; Kallikreins/therapeutic use* ; Male ; Muscle, Smooth, Vascular/physiopathology* ; Nitric Oxide Synthase Type I/metabolism* ; Nitric Oxide Synthase Type III/metabolism* ; Penile Erection/physiology* ; Penis/metabolism* ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate/therapeutic use* ; Treatment Outcome ; Urological Agents/therapeutic use*

Objective: To evaluate the safety, efficacy and tolerability of China-made sildenafil citrate (Jinge) in the treatment of ED. METHODS: We conducted a multi-center, randomized, double-blind and placebo-controlled clinical trial among 222 ED patients in five urological or andrological clinics of China. The patients were randomly assigned to receive sildenafil citrate (SC, n = 111) or placebo (n = 111) for 8 weeks. We obtained and analyzed the demographic and clinical characteristics of the patients, the scores of International Index of Erectile Function (IIEF), the success rate of sexual intercourse, and the incidence of adverse events. RESULTS: No statistically significant differences were found between the patients of the SC and those of the placebo group in the mean age (［47.2±11.32］ yr vs ［46.67±13.08］ yr, P>0.05), psychological etiology (27.93% vs 23.42%, P>0.05), organic etiology (21.62% vs 29.73%, P>0.05) or mixed etiology (50.45% vs 46.85%, P>0.05), nor in height, weight, nationality, or history of smoking, drinking or allergy. Compared with the placebo controls, the SC-treated patients showed significant increases in the excellence rate of effectiveness (29.91% vs 78.90%, P<0.01), success rate of sexual intercourse (29.16% vs 63.87%, P<0.01), and total effectiveness rate (34.58% vs 77.98%, P<0.01). The effectiveness rates on organic, psychogenic and mixed types ED were remarkably higher in the SC group (64.52%, 83.33%, and 82.14%) than in the placebo control (46.15%, 21.21%, and 25.00%) (P<0.01). Mild or temporary adverse events were observed in 32 cases in the SC group as compared with 13 in the placebo control. CONCLUSIONS China-made sildenafil citrate is an effective, safe and well-tolerated drug for ED of different etiologies in the Chinese population.
Aged ; China ; Coitus ; Double-Blind Method ; Drug Compounding ; Erectile Dysfunction ; drug therapy ; etiology ; Humans ; Male ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Sildenafil Citrate ; therapeutic use ; Smoking ; Treatment Outcome

Objective: To make a real-world study on the efficacy and safety of traditional Chinese medicine (TCM) combined with sildenafil in the treatment of erectile dysfunction (ED) that failed to respond to TCM medication. METHODS: This study included 1 038 ED patients with the International Index of Erectile Function-5 (IIEF-5) scores ≤21 and improvement <30% after 4 weeks of TCM medication, differentially diagnosed with kidney-yang or kidney-yin deficiency syndrome. We administered TCM combined with sildenafil (Viagra, Pfizer Pharmaceutical Co., Ltd) at 100 mg 1 hour before sexual intercourse. After 2 and 4 weeks of medication, we recorded the scores in IIEF-5, erection hardness, Sexual Encounter Profile question 2 (SEP-2: whether vaginal penetration is successful), SEP-3 (whether sexual intercourse is successful), and TCM Syndromes Scale as well as the indexes of routine blood, urine, liver function, and renal function of the patients, and compared them with those obtained before treatment. RESULTS: No serious adverse reactions were observed in any of the patients. Compared with the baseline, the patients achieved significantly increased IIEF-5 scores after 2 and 4 weeks of medication (15.01 ± 2.25 vs 16.96 ± 2.55 and 19.41 ± 2.82, P <0.05), penileelectionhardness remarkably improved at 4 weeks (3.36% vs 44.58%, P<0.05), and the positive answers to SEP-2 and SEP-3 both markedly increased at 2 (38.11% vs 90.49%, P<0.05; 22.01% vs 63.77% , P<0.05) and 4 weeks (38.11% vs 96.95% , P<0.05; 22.01% vs 89.73%, P<0.05). CONCLUSIONS TCM combined with sildenafil is safe and effective in the treatment of ED in Chinese men, which can significantly improve the IIEF-5 score and erection hardness of the patients.
Aged ; Asian Continental Ancestry Group ; Coitus ; Drug Therapy, Combination ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; drug therapy ; etiology ; Humans ; Male ; Medicine, Chinese Traditional ; Penile Erection ; drug effects ; physiology ; Sildenafil Citrate ; therapeutic use ; Treatment Outcome ; Yang Deficiency ; complications ; Yin Deficiency ; complications

Objective: To investigate the safety and efficacy of pancreatic kininogenase combined with sildenafil in the treatment of erectile dysfunction(ED) in type 2 diabetes mellitus (DM) patients in the high-altitude area. METHODS: This study included 93 ED patients with type 2 DM, all residents of the Xining area 1500 meters above sea level. We randomly divided them into an experimental group (n = 48) and a control group (n = 45), the former treated with pancreatic kininogenase(120 u, tid) and sildenafil (25 mg, qd at bedtime), while the latter with sildenafil only (25 mg, qd at bedtime).After 4 and 8 weeks of medication, we obtained the penile hemodynamic parameters,IIEF-5 scores, and sexual intercourse satisfaction(SIS) scores and compared them between the two groups of patients. RESULTS: There were no statistically significant differences in age or DM course between the two groups of patients (P >0.05).Compared with the baseline, both the experimental and control groups showed remarkably improvement inthe IIEF-5 score (8.81 ± 2.06 vs 11.54 ± 7.72 and 8.29 ± 1.91 vs 9.37± 1.65, P <0.05), SIS score (3.35 ± 2.43vs6.83± 2.61and 3.41 ± 2.38 vs 4.92± 2.49, P <0.05), and penile hemodynamic parameters obtained by color duplex Doppler ultrasonography(P <0.05), with significant differences between the two groups in the IIEF-5 score (11.54 ± 7.72 vs 9.37± 1.65, P <0.05) and SIS score (6.83± 2.61 vs 4.92± 2.49, P <0.05) but not in the penile hemodynamic parameters (P >0.05). Even more remarkable improvement was observed at 8 weeks in the experimental and control groups in the IIEF-5 score (19.29± 1.85 and 15.43± 1.74)(P <0.05), SIS score (11.73 ± 2.57 and 6.55± 2.71) (P <0.05), and penile hemodynamic parameters(P <0.05), all with significant differences between the two groups (P <0.05). CONCLUSIONS Pancreatic kininogenase combined with sildenafil has a better clinical effect than sildenafil alone on ED in type 2 DM patientsin the high-altitude area.
Aged ; Altitude ; Coitus ; Diabetes Mellitus, Type 2 ; complications ; Drug Therapy, Combination ; Erectile Dysfunction ; etiology ; therapy ; Humans ; Kallikreins ; therapeutic use ; Male ; Pancreas ; enzymology ; Penile Erection ; drug effects ; physiology ; Penis ; physiology ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Sildenafil Citrate ; therapeutic use ; Treatment Outcome

OBJECTIVETo search for the optimal strategies for sperm collection from the patient with temporary penile erectile dysfunction (ED) on the day of oocyte pick-up ( OPU) in in vitro fertilization embryo transfer (IVF-ET).

METHODSWe retrospectively analyzed 93 cases of temporary ED on the OPU day of IVF-ET from January 2011 to May 2014, with fresh semen for 45 cases (group A), cryopreserved sperm before oocyte retrieval for 30 cases (group B), and frozen oocytes for 18 cases (group C). Group A was again subdivided into A1 (n = 18) and A2 n = 27) , the former intervened with oral sildenafil while the latter left untreated. We compared the rates of fertilization, high-quality embryo, and pregnancy among different groups.

RESULTSNo statistically significant differences were found among groups A, B and C in the age of the males and females, duration of infertility, numbers of obtained and mature oocytes, and rates of cleavage, or in the percentages of normal fertilization (80.78% vs 80.43% vs 84.77%), high-quality embryo (53.27% vs 52.97% vs 47.69%) and pregnancy (60.00% vs 56.77% vs 44.44%) (all P > 0.05). The rate of 3PN was markedly lower in group C (0.63%) than in A (9. 61%) and B (4.34%) (P < 0.05). There were no significant differences between groups A1 and A2 in the age of the males and females, duration of infertility, numbers of obtained and mature oocytes, and the rates of fertilization, cleavage, high-quality embryo, and pregnancy (all P > 0.05).

CONCLUSIONOn the OPU day of IVF-ET, oral sildenafil can help temporary ED men to achieve penile erection and ejaculation without affecting the outcomes of assisted reproduction. Cryopreserved sperm can be used in case of predicted temporary ED and frozen oocytes can also be employed if sperm retrieval fails. However, to avoid puncture injury to the epididymis or testis, fresh semen should be the first choice.

Cryopreservation ; Embryo Transfer ; Erectile Dysfunction ; drug therapy ; physiopathology ; Female ; Fertilization ; Fertilization in Vitro ; Humans ; Male ; Oocyte Retrieval ; Oocytes ; Penis ; Pregnancy ; Retrospective Studies ; Sildenafil Citrate ; therapeutic use ; Sperm Retrieval ; Spermatozoa

OBJECTIVE: To study the effects of sildenafil on morphology to noise-induced hearing loss in guinea pigs. METHOD: Guinea pigs were randomly divided into control group, noise exposure group and the sildenafil treatment group, 12 in each group. a week after white noise exposure of 110 dB, sildenafil (10 mg/kg x d) and NS (4 ml/kg x d) were injected into guinea pigs of the sildenafil treatment group and noise exposure group respectively for four continuous weeks. ABR thresholds were measured respectively prior to the experiment, 1 week post-noise, 1, 2 and 4 weeks post-drugs, the changes of cochlea hair cells were also observed with a scan electron microscope (SEM) and light microscope. RESULT: The ABR threshold shifts in the sildenafil treatment group were significantly fewer than that in the noise exposure group. SEM showed that hear hair of the inner and outer hair cells in noise exposure group displayed mess, fusion and imperfections. In the sildenafil treatment group, the hair cells displayed slight pathological changes, there wasn't significant differents comparied with normal group. The number of OHCs were relatively stable in the normal group, while the obvious OHC loss was observed in other groups. There was significant difference among the three groups, however, the OHC loss in the sildenafil treatment group was not significantly different to that in the noise exposure (P > 0.05). CONCLUSION Sildenafil can significantly protect against noise-induced hearing loss.
Animals ; Guinea Pigs ; Hair Cells, Auditory, Outer ; drug effects ; pathology ; Hearing Loss, Noise-Induced ; drug therapy ; Noise ; Sildenafil Citrate ; therapeutic use

OBJECTIVETo observe the clinical efficacy and safety of sildenafil in the treatment of high altitude heart disease associated with severe pulmonary arterial hypertension (PAH) in children.

METHODSFifty children (aged 2 months to 2 years) with high altitude heart disease associated with severe PAH, who were continuously transferred to the Intensive Care Unit between January 2011 and October 2013, were randomly assigned to observation and control groups. The control group was given conventional treatment, while the observation group received oral sildenafil [1 mg/(kg . d)] three times daily for 7-10 days in addition to the conventional treatment. Before and after treatment, hemodynamics, blood gas, routine blood parameters, and blood biochemical parameters were recorded.

RESULTSAfter treatment, the observation group had a significantly higher decrease in mean pulmonary artery pressure and significantly higher increases in arterial partial pressure of oxygen, cardiac output, cardiac index, and oxygenation index compared with the control group (P<0.05). In the observation group, there were no significant changes in mean arterial pressure, routine blood parameters and blood biochemical parameters (P>0.05), and no obvious adverse reactions were found.

CONCLUSIONSFor children with high altitude heart disease associated with severe PAH, sildenafil can effectively reduce pulmonary artery pressure and improve cardiac function and does not cause adverse reactions. This therapy has good safety according to the preliminary evaluation.

Altitude ; Familial Primary Pulmonary Hypertension ; Female ; Heart Diseases ; drug therapy ; Humans ; Hypertension, Pulmonary ; complications ; physiopathology ; Infant ; Male ; Piperazines ; adverse effects ; therapeutic use ; Purines ; adverse effects ; therapeutic use ; Sildenafil Citrate ; Sulfones ; adverse effects ; therapeutic use ; Vasodilator Agents ; adverse effects ; therapeutic use

OBJECTIVETo investigate the effect of Bushengzhuyang Fang (Yangjing Capsule, YJC) on penile erectile function and its action mechanisms in rats.

METHODSFifty-six male SD rats were randomly divided into seven groups of equal number: blank control, daidzein, daidzein + testosterone, daidzein + sildenafil, daidzein + low-dose YJC, daidzein + medium-dose YJC, and daidzein + high-dose YJC. The rats in the blank control group were treated intragastrically with normal saline and those in the other groups with daidzein at the dose of 100 mg per kg per day for 30 days. Then the last five groups received additionally testosterone (4 mg per kg per day), sildenafil (2.5 mg per kg per day), low-dose YJC, (0.315 mg per kg per day), medium-dose YJC (0.63 mg per kg per day), and high-dose YJC (1. 26 mg per kg per day), respectively. At 0, 30 and 60 days of treatment, we observed the apomorphine-induced spontaneous erectile response and pathological changes in the corpus cavernosum of the rats, recorded the number of penile erection and erectile incubation period, and determined the serum levels of testosterone (T) and luteinizing hormone (LH).

RESULTSAt 30 days of treatment, the number of apomorphine-induced erections was decreased, the erectile incubation period prolonged, and the serum levels of T and LH reduced remarkably in all groups of rats (P < 0.05). Compared with the findings at 30 days, the number of penile erections was significantly decreased at 60 days in the daidzein group (1.39 ± 0.42 vs 2.67 ± 0.33, P < 0.05) and daidzein + low-dose YJC group (1.33 ± 0.49 vs 2.83 ± 0.61, P < 0.05); the erectile incubation period was markedly ex- tended ([16.33 ± 3.11] vs [8.50 ± 0.93] min and [15.50 ± 3.21] vs [8.63 ± 1.54] min, P < 0.05); and the serum levels of T ([5.34 ± 0.89] vs [1.24 ± 0.30] ng/ml and [5.28 ± 1.12] vs [2.07 ± 0.76] ng/ml, P < 0.05) and LH ([3.62 ± 0.37] vs [2.09 ± 0.12] ng/ml and [3.79 ± 0.28] vs [2.17 ± 0.33] ng/ml, P < 0.05) were significantly reduced in the daidzein and daidzein + low-dose YJC groups, respectively. Pathological examination revealed slightly decreased cavernous sinuses and blood vessels in the corpus cavernosum of the rats in the daidzein + testosterone, daidzein + sildenafil, daidzein + medium-dose YJC, and daidzein + high-dose YJC groups as compared with those in the blank control group.

CONCLUSIONHigh-dose Yangjing Capsule is efficacious for the recovery of erectile function in rats, especially for phytoestrogen-induced erectile dysfunction.

Animals ; Apomorphine ; pharmacology ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; chemically induced ; drug therapy ; Humans ; Isoflavones ; pharmacology ; Luteinizing Hormone ; Male ; Penile Erection ; drug effects ; physiology ; Penis ; drug effects ; pathology ; Phytoestrogens ; Phytotherapy ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate ; Sulfonamides ; therapeutic use ; Testosterone ; therapeutic use ; Vasodilator Agents ; therapeutic use