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

The aim of this study was to investigate whether the omega-3 fatty acids help to improve erectile function in an atherosclerosis-induced erectile dysfunction rat model. A total of 20 male Sprague-Dawley rats at age 8 weeks were divided into three groups: Control group (n = 6, untreated sham operated rats), Pathologic group (n = 7, untreated rats with chronic pelvic ischemia [CPI]), and Treatment group (n = 7, CPI rats treated with omega-3 fatty acids). For the in vivo study, electrical stimulation of the cavernosal nerve was performed and erectile function was measured in all groups. Immunohistochemical antibody staining was performed for transforming growth factor beta-1 (TGF-β1), endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor 1-alpha (HIF-1α). In vivo measurement of erectile function in the Pathologic group showed significantly lower values than those in the Control group, whereas the Treatment group showed significantly improved values in comparison with those in the Pathologic group. The results of western blot analysis revealed that systemically administered omega-3 fatty acids ameliorated the cavernosal molecular environment. Our study suggests that omega-3 fatty acids improve intracavernosal pressure and have a beneficial role against pathophysiological consequences such as fibrosis or hypoxic damage on a CPI rat model, which represents a structural erectile dysfunction model.
Animals ; Atherosclerosis/*complications ; Blotting, Western ; Carotid Arteries/physiology ; Chronic Disease ; Disease Models, Animal ; Electric Stimulation ; Fatty Acids, Omega-3/*pharmacology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Ischemia/etiology/*pathology ; Male ; Nitric Oxide Synthase Type III/metabolism ; Penile Erection/*drug effects ; Penis/metabolism/pathology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1/metabolism

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

OBJECTIVETo investigate the effect of salidroside on hypoxia-induced apoptosis of corpus cavernosum smooth muscle cells (CCSMCs) in rats.

METHODSRat CCSMCs were cultured in vitro by the enzyme digestion method and identified by immunofluorescent staining of anti-alpha-SMA and anti-Desmin. The non-toxic dose of salidroside was determined by MTT assay. Low-oxygen mixed gas (1% O2, 5% CO2, and 94% N2) was piped into a modular incubator chamber to induce hypoxia. The CCSMCs were divided into a normal, a hypoxia, and a 32 microg/mL salidroside intervention group. The apoptosis of the CCSMCs was detected by flow cytometry and the expression of the caspase-3 protein determined by Western blot.

RESULTSThe majority of the CCSMCs were positive for alpha-SMA and Desmin at immunofluorescent staining. Salidroside at < 32 microg/ml produced no obvious toxicity to CCSMCs. Compared with the normal control group, the rates of early and late apoptosis of CCSMCs were both increased significantly in the hypoxia group ([12.77 +/-1.41]% vs [18.69 +/- 1.29]%, P < 0.01 and [14.63 +/- 2.00]% vs [21.03 +/- 1.530]% , P < 0.05). Western blot showed a markedly increased expression of cleaved caspase-3 (P < 0.01). Intervention with 32 microg/ml salidroside significantly reduced hypoxia-induced early apoptosis of CCSMCs ([13.46% +/- 1.87]%, P < 0.01) and decreased the expression of cleaved caspase-3 (P < 0.01).

CONCLUSIONSalidroside can reduce the expression of cleaved caspase-3 and inhibit hypoxia-induced apoptosis of CCSMCs in rats.

Animals ; Apoptosis ; drug effects ; physiology ; Caspase 3 ; metabolism ; Cell Hypoxia ; physiology ; Cells, Cultured ; Glucosides ; pharmacology ; Humans ; Male ; Myocytes, Smooth Muscle ; cytology ; drug effects ; enzymology ; Penis ; cytology ; drug effects ; Phenols ; pharmacology ; Rats

OBJECTIVETo investigate the ultrasonographic indexes in the evaluation of complete penile erection after oral administration of sildenafil citrate in men with normal erectile function.

METHODSThe subjects lay supine, with the penis raised upwards, its back clinging to the abdomen. The probe was placed at the base of the ventral side of the penis for longitudinal and transverse section scanning. Observations were made on the corpus cavernosum, deep artery and deep dorsal vein of the penis at the time of flaccidity and complete erection after oral administration of sildenafil citrate, respectively.

RESULTSThe examinations were acceptable to all the subjects both physically and psychologically, and all were completed successfully with no complications. Compared with the flaccid state of the penis, obvious changes were observed in the state of complete erection, including marked increases in the diameter of the corpus cavernosum ([18.57 +/- 2.50] mm, increased by [106.8 +/- 62.1]%), the inside diameter of the deep artery ([1.18 +/- 0.26] mm, increased by [54.9 +/- 29.0]%), the peak systolic velocity ([32.5 +/- 10.7] cm/s, increased by [209.3 +/- 112.9]%), and the systolic acceleration ([5.71 +/- 2.71] cm/s2, increased by [179.3 +/- 138.2]%).

CONCLUSIONOral administration of sildenafil citrate followed by ultrasonography is a new approach to the objective evaluation of penile erection, characterized by convenience, safety, non-invasiveness, non-complication, easy acceptability and easy clinical application.

Adult ; Humans ; Male ; Penile Erection ; drug effects ; physiology ; Penis ; diagnostic imaging ; Piperazines ; pharmacology ; Purines ; pharmacology ; Sildenafil Citrate ; Sulfones ; pharmacology ; Ultrasonography

AIMTo explore the mechanism of chronic renal failure (CRF)-related erectile dysfunction (ED).

METHODSCRF experimental models were established by 5/6 nephrectomy from male Sprague-Dawley rats. Both the rats from the control group (NCRF group, n=6) and the experimental group (CRF group, n=30) were injected with a low dose (80 microg/kg) of apomorphine in the 12th week after resection surgery to measure corresponding penile erections. Western blot method was thereafter conducted to measure the expression of connexin 43 (CX43) in the rat corpus cavernosum in the 12th week after the resection surgery.

RESULTSThere was one death in the NCRF group and five in the CRF group. The penile erection ratio of the CRF group was 28% (7/25), whereas that of the NCRF group was 100% (5/5), which presents a significant difference between the two groups (P < 0.05). In terms of penile erection frequency, the average of the CRF group was 1.0 +/- 0.0, which was significantly different from that of the NCRF group (2.2 +/- 0.8) (P < 0.05). As for the expression of CX43 in the rat corpus cavernosum, a notable difference existed between the CRF group (0.21 +/- 0.07) and the NCRF group (0.53 +/- 0.27) (P < 0.01).

CONCLUSIONCRF significantly reduces the erectile function of rats. A close correlation exists between the expression of CX43 in rats' corpus cavernosum and CRF-related ED.

Animals ; Apomorphine ; pharmacology ; Blotting, Western ; Connexin 43 ; genetics ; Disease Models, Animal ; Erectile Dysfunction ; genetics ; Gene Expression ; Kidney Failure, Chronic ; complications ; Male ; Penile Erection ; drug effects ; physiology ; Penis ; enzymology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of alcohol intake on penile structure and function in rats.

METHODSThirty adult male Wistar rats were randomly divided into two groups: control group and alcohol intake group. They were administered with 2 mL of normal saline and 40% alcohol solution respectively through gastric tubes every day. Three months later, the animal model of alcohol intake was evaluated by modified Nayagida's method, and the effects of alcohol on the rats were studied by sexual behavior, the number of apomorphine-induced penile erection, level of testosterone in the sera, and the content of penile smooth muscle.

RESULTSThe scores of animal model of alcohol intake evaluated by Nayagida's method were 0.66 +/- 2.05 in the control group and 9.26 +/- 5.50 in the alcohol intake group (P < 0.05), which indicated that an animal model of alcohol intake was successfully established. Sexual behavior, the number of apomorphine-induced penile erection, testosterone level in the sera, and the content of penile smooth muscle of the alcohol intake group were all statistically different as compared with the control group (P < 0.05).

CONCLUSIONAlcohol intake induces sexual dysfunction in rats, which may be due to the decline of testosterone level in the sera and decline of penile smooth muscle.

Animals ; Ethanol ; adverse effects ; Female ; Male ; Penis ; anatomy & histology ; drug effects ; physiology ; Rats ; Rats, Wistar ; Sexual Behavior, Animal ; Testosterone ; blood

OBJECTIVETo study the relaxant effect of ethanol on the isolated rabbit corpus cavernosum and its possible mechanism.

METHODSThe tension of isolated smooth muscle strips was recorded by the platform physiological graphed, and the concentrations of cAMP and cGMP in the rabbit corpus cavernosum were measured by 125I radioimmunoassay.

RESULTSThe 1.25% (V/V) ethanol significantly augmented the corporal relaxation induced by isoprenaline (10(-9) - 10(-5) mol/L). Ethanol-induced relaxation was inhibited by 100 micromol/L and 300 micromol/L SQ22536 (an adenylate cyclase inhibitor). Emax was depressed from (105.12 +/- 3.39) % to (97.00 +/- 2.57) % in the presence of 100 micromol/L SQ22536 or (91.09 +/- 2.42) % in the presence of 300 micromol/L SQ22536. EC50 was increased from (1.18 +/- 0.09)% (V/V) to (1.36 +/- 0.10) % in the presence of 100 micromol/L SQ22536 (P < 0.05) or (1.68 +/- 0.13) % (in the presence of 300 micromol/L SQ22536) (P < 0.05) respectively. Ethanol significantly elevated the level of cAMP but not that of cGMP in the isolated rabbit corpus cavernosum, and it also significantly enhanced the activity of the adenylate cyclase (AC) extracted from the rabbit corpus cavernosum in a dose-dependent manner.

CONCLUSIONEthanol has a relaxant effect on the isolated rabbit corpus cavernosum, which may be associated with the cAMP signaling pathway.

Animals ; Central Nervous System Depressants ; pharmacology ; Cyclic AMP ; metabolism ; Ethanol ; pharmacology ; In Vitro Techniques ; Male ; Muscle Relaxation ; drug effects ; Penile Erection ; drug effects ; physiology ; Penis ; drug effects ; physiology ; Rabbits ; Signal Transduction ; drug effects

AIMTo investigate the relaxation mechanisms of neferine (Nef) on the rabbit corpus cavernosum tissue in vitro.

METHODSStrips of rabbit corpus cavernosum were mounted in organ chambers. The effects of Nef were examined on isolated muscle strips precontracted with phenylephrine (PE) alone, in the presence of N(W)-nitro-L-arginine (LNNA, a nitric oxide synthase inhibitor), 1-H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor), indomethacin (cyclooxygenase inhibitor), tetraethylammonium (Ca(2+)-activated K(+) channel blocker), 4-aminopiridine (4-AP, voltage dependent K(+) channel blocker) and glibenclamide (ATP sensitive K(+) channel blocker). The effects of Nef on KCl-induced contraction of isolated muscle strips were also investigated. The procedure of calcium absence-calcium addition was designed to observe the effect of Nef on two components of the contractile responses to PE based on the source of Ca(2+) (extracellular vs. intracellular).

RESULTSCorpus cavernosum strips relaxed in response to Nef (10(-9)-10(-4) mol/L) in a concentration-dependent manner with an IC(50) of 4.60 X 10(-6) mol/L. However, they were not affected by LNNA, ODQ, indomethacin or K(+)-channel blockers. Nef (10(-6) mol/L, 10(-5) mol/L) concentration dependently reduced the maximal contraction response of isolated strips induced by KCl to 79.3%+/-5.5% and 61.5%+/-3.2%, respectively (P < 0.01). In the calcium absence-calcium addition procedure, Nef 10(-5) mol/L inhibited both intracellular calcium-dependent and extracellular calcium-dependent contraction induced by PE (2 X 10(-5) mol/L) (P < 0.05). The inhibition ratios were 26.2%+/-5.4% and 48.3%+/-7.6%, respectively.

CONCLUSIONThe results of the present study suggest that Nef possesses a relaxant effect on rabbit corpus cavernosum tissues, which is attributable to the inhibition of extracellular Ca2+ influx and the inhibition of release of intracellular stored Ca(2+), but not mediated by the release of nitric oxide, prostaglandins or by the activation of potassium channels.

Animals ; Benzylisoquinolines ; pharmacology ; Calcium ; pharmacology ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Male ; Muscle Contraction ; drug effects ; Muscle Relaxation ; drug effects ; Penis ; drug effects ; physiology ; Phenylephrine ; pharmacology ; Potassium Chloride ; pharmacology ; Rabbits ; Vasoconstrictor Agents ; pharmacology

OBJECTIVETo study the effect of endogenous carbon monoxide (CO) on the smooth muscle function of the dog penile corpus cavernosum in vitro.

METHODSTissue bioassay was used to measure the corpus cavernosum muscle contraction and relaxation. The production of CO was induced in the corpus cavernosum smooth muscle, and the effect of CO on the penile corpus cavernosum smooth muscle pre-contracted by phenylephrine (PE) was determined.

RESULTSChlorinous hemoglobin could relax the smooth muscle stripes pre-contracted by 10 micromol/L PE. A dose-dependent relaxation was observed. The relaxation responses by 10 -100 micromol/L chlorinous hemoglobin were significant compared with the control group (P < 0. 01). The pretreatment of the muscle stripes with ZnPP-IX or methylthioninium significantly reduced the relaxing effect of chlorinous hemoglobin (P < 0.01).

CONCLUSIONThe relaxing effect of endogenous CO on the smooth muscle of the penile corpus cavernosum depends on the concentration of endogenous CO. The underlying mechanism may involve the pathway from CO to cGMP production.

Animals ; Carbon Monoxide ; physiology ; Dogs ; Dose-Response Relationship, Drug ; Hemin ; pharmacology ; In Vitro Techniques ; Male ; Muscle, Smooth ; drug effects ; physiology ; Penile Erection ; drug effects ; physiology ; Penis ; drug effects ; physiology