Proteomic analysis of oxidative stress response in human umbilical vein endothelial cells (HUVECs): role of heme oxygenase 1 (HMOX1) in hypoxanthine-induced oxidative stress in HUVECs.

BACKGROUND: Erectile dysfunction (ED) is a well-known complication of diabetes, affecting up to 75% of diabetic men. Although the etiology of diabetic ED is multifactorial, endothelial dysfunction is considered to be a pillar of its pathophysiology. Endothelial dysfunction is caused by the harmful effects of high glucose levels and increased oxidative stress on the endothelial cells that comprise the vascular endothelium. The aim of this study was to identify the proteomic changes caused by high glucose-induced oxidative stress and explore the role of heme oxygenase 1 (HMOX1) in it. METHODS: The cellular proteomic response to hypoxanthine-induced oxidative stress in human umbilical vein endothelial cells (HUVECs) was analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were analyzed through Network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Further validation assays was performed to validate the role of HMOX1. RESULTS: The results showed that 66 and 76 DEPs were markedly upregulated and downregulated, respectively, for HUVECs oxidative stress. Among these proteins, we verified eight dysregulated genes by quantitative reverse transcription PCR, including nucleolin (NCL), X-ray repair cross-complementing protein 6 (XRCC6), ubiquinol-cytochrome C reductase binding protein (UQCRB), non-POU domain containing octamer binding (NONO), heme oxygenase 1 (HMOX1), nucleobindin 1 (NUCB1), DEK, and chromatin target of prmt1 (CHTOP). Further, using overexpression and genetic knockdown approaches, we found that HMOX1 was critical for the oxidative stress response in HUVECs. CONCLUSIONS: We found that HMOX1 was closely related to the oxidative stress response induced by hypoxanthine. To the best of our knowledge, this study is the first overview of the responses of HUVECs to oxidative stress. The findings will contribute to analyses of the detailed molecular mechanisms involved in the pathogenesis of endothelial dysfunction and related molecular mechanisms in ED patients.

Total triterpenoids from Ganoderma Lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis.

In this study, one immortalized human normal prostatic epithelial cell line (BPH) and four human prostate cancer cell lines (LNCaP, 22Rv1, PC-3, and DU-145) were treated with Ganoderma Lucidum triterpenoids (GLT) at different doses and for different time periods. Cell viability, apoptosis, and cell cycle were analyzed using flow cytometry and chemical assays. Gene expression and binding to DNA were assessed using real-time PCR and Western blotting. It was found that GLT dose-dependently inhibited prostate cancer cell growth through induction of apoptosis and cell cycle arrest at G1 phase. GLT-induced apoptosis was due to activation of Caspases-9 and -3 and turning on the downstream apoptotic events. GLT-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and E2F1 expression at the late time. These findings demonstrate that GLT suppresses prostate cancer cell growth by inducing growth arrest and apoptosis, which might suggest that GLT or Ganoderma Lucidum could be used as a potential therapeutic drug for prostate cancer.

Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase.

Prostate cancer is the most commonly diagnosed non-cutaneous cancer and one of the leading causes of cancer death for North American men. Whereas localized prostate cancer can be cured, there is currently no cure for metastatic prostate cancer. Here we report a novel approach that utilizes designed chimeric transcription activator-like effectors (dTALEs) to control prostate cancer metastasis. Transfection of dTALEs of DNA methyltransferase or demethylase induced artificial, yet active locus-specific CpG and subsequent histone modifications. These manipulations markedly altered expression of endogenous CRMP4, a metastasis suppressor gene. Remarkably, locus-specific CpG demethylation of the CRMP4 promoter in metastatic PC3 cells abolished metastasis, whereas locus-specific CpG methylation of the promoter in non-metastatic 22Rv1 cells induced metastasis. CRMP4-mediated metastasis suppression was found to require activation of Akt/Rac1 signaling and down-regulation of MMP-9 expression. This proof-of-concept study with dTALEs for locus-specific epigenomic manipulation validates the selected CpG methylation of CRMP4 gene as an independent biomarker for diagnosis and prognosis of prostate cancer metastasis and opens up a novel avenue for mechanistic research on cancer biology.

Rare earths exposure and male infertility: the injury mechanism study of rare earths on male mice and human sperm.

The weight; testis/body coefficient; levels of LDH, SDH, SODH, G-6PD, and testosterone; cell cycle; and cell apoptosis of the male mice were influenced after being treated with 200 mg/[kg/day] of rare earths suspension for 3 weeks. The "Raman fingerprints" of the human sperm DNA exposed to 0.040 mg/ml CeCl3 were very different from those of the untreated; the Raman bands at 789 cm(-1) (backbone phosphodiester), PO4 backbone at 1,094 cm(-1), methylene deformation mode at 1,221 cm(-1), methylene deformation mode at 1,485 cm(-1), and amide II at 1,612 cm(-1), of which intensities and shifts were changed, might be the diagnostic biomarkers or potential therapeutic targets. The injury mechanism might be that the rare earths influence the oxidative stress and blood testosterone barrier, tangle the big biomolecule concurrently, which might cause the testicular cells and vascular system disorder and/or dysfunction, and at the same time change the physical and chemical properties of the sperm directly.

Antioxidative protective effect of icariin on the FeSO4/H 2O 2-damaged human sperm based on confocal raman micro-spectroscopy.

Oxidative stress is implicated in male infertility and significantly higher reactive oxygen species are detected in 25% of infertile males. Although different agents of various alternative medicines, including traditional Chinese medicine, have been tried with varying success, evidence remains limited on whether and how much herbs or supplements might help increase the anti-oxidant ability of the sperm. This study examined the anti-oxidative effects of icariin, a flavonoid isolated from Herba Epimedii, on the human sperm. We prepared the FeSO4/H2O2-damaged human sperms, which were co-cultured with icariin in vitro, and then observed the changes of the sperm by employing Raman micro-spectroscopy. The results showed that Raman mapping with a 514 nm excitation laser allowed clear differentiation of the nucleus, neck, and, in particular, the mitochondria-rich middle piece of a human sperm cell. The effect of icariin on different organelles of the sperm was quantified by localized spectral Raman signatures obtained within milli-seconds, and icariin could keep the "Raman fingerprint" of the human sperm the same as the control groups, suggesting that icariin could protect the human sperm from being damaged by FeSO4/H2O2. Icariin may serve as a tonifying and replenishing agent of herbal origin for enhancing reproductive functions.

Did prostate size affect the complication and outcome of plasmakinetic enucleation of the prostate?

OBJECTIVE: To evaluate surgical complications and outcomes based on prostate size in patients with benign prostatic hyperplasia (BPH) treated with plasmakinetic enucleation of the prostate (PKEP). METHODS: A retrospective review was conducted of PKEP performed between July 2008 and January 2013. According to the prostate size on preoperative transrectal ultrasonography measurement, patients were divided into three groups: group 1: <40 ml, group 2: 40-80 ml and group 3: >80 ml. Baseline, perioperative and postoperative data were obtained. RESULTS: There were significant differences among the three groups regarding the mean operative time (p < 0.001) and the mean resected tissue weight (p < 0.001). But enucleation efficiency (p < 0.001) in gm tissue per minute increased significantly as prostate size increased. Mean hemoglobin decrease (p > 0.05), mean postoperative irrigation time (p > 0.05), mean catheter time (p > 0.05) and mean hospital stay (p > 0.05) did not differ significantly among three groups. The three groups had a similar and significant postoperative improvement in International Prostate Symptom Score, quality of life, maximum uroflow rate and post-void residual urine volume independent of prostate size (p < 0.001), but no significant difference was found among three groups at the 12-month follow-up (p > 0.05). Perioperative and postoperative complications did not depend on prostate size (p > 0.05). CONCLUSIONS: Although patients with a larger BPH required significantly longer operation time in PKEP, prostate size did not affect perioperative and postoperative complications or micturition improvement.

shRNA constructs targeting IGFBP-3 alleviate age related erectile dysfunction in the rat.

PURPOSE: We investigated whether injecting shRNA constructs targeting IGFBP-3 in the penis of old rats would improve erectile function. MATERIALS AND METHODS: The most validated IGFBP-3 shRNA plasmid vector (pGPU6/GFP/Neo-shIGFBP-3) was prepared and injected in penile corpus cavernosum tissue. A total of 30 old (age 24 months) male Sprague Dawley® rats were randomly divided into 3 groups, including 10 each that received phosphate buffered saline only (100 µl), pGPU6/GFP/Neo-shNC (100 µg) and the most validated plasmid constructs pGPU6/GFP/Neo-shIGFBP-3 (100 µg). At 4 weeks the erectile response was measured as intracavernous pressure. The percent of smooth muscle in corpus cavernosum tissue was evaluated. Nitric oxide synthase activity and the cGMP concentration in penile tissue were also analyzed. IGFBP-3 was estimated in penile tissue by Western blot, real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. RESULTS: pGPU6/GFP/Neo-shIGFBP-3 corrected the impaired erectile response in aged rats compared with the response in those injected with phosphate buffered saline and pGPU6/GFP/Neo-shNC (each p <0.01). The percent of cavernous smooth muscle was increased in the pGPU6/GFP/Neo-shIGFBP-3 group. Nitric oxide synthase activity and the cGMP concentration were also significantly increased in rats treated with pGPU6/GFP/Neo-shIGFBP-3. IGFBP-3 shRNA effectively reduced IGFBP-3 mRNA and protein expression in penile corpus cavernosum tissue. CONCLUSIONS: Decreasing IGFBP-3 expression by plasmid expressed shRNA improved erectile function in aged rats. The therapy may modulate smooth muscle integrity and increase the cGMP concentration. This may be a new direction for treating erectile dysfunction in clinical practice.

Loupe-assisted versus microscopic varicocelectomy: is there an intraoperative anatomic difference?

The aim of this study was to compare the intraoperative difference in anatomic details between loupe-assisted and microscopic varicocelectomy within the same spermatic cord. Between April 2011 and August 2011, 26 men with 33 sides containing grade 2-3 varicocele were enrolled in this study. First, one surgeon performed the open inguinal varicocelectomy under × 3.5 loupe magnification. The presumed vascular channels and lymphatics were isolated and marked without ligation. Another surgeon then microsurgically dissected and checked the same spermatic cord using an operating microscope to judge the results in terms of the ligation of the internal spermatic veins and the preservation of the arteries and lymphatics. There were significant differences in the average number of internal spermatic arteries (1.51 vs 0.97), internal spermatic veins (5.70 vs 4.39) and lymphatics (3.52 vs 1.61) between the microscope and loupe-assisted procedures (P < 0.001, P < 0.001, P < 0.001, respectively). Meanwhile, in varicocele repair with loupe magnification, an average of 1.30 ± 1.07 (43/33) internal spermatic veins per side were missed, among the overlooked veins, 1.12 ± 0.93 (37/33) were adhered to the preserved testicular artery, as well as 0.55 ± 0.79 lymphatics and 0.36 ± 0.55 arteries that were to be ligated. In conclusion, microscopic varicocelectomy could preserve more internal spermatic arteries and lymphatics and could ligate more veins than the loupe-assisted procedure. To some degree, loupe magnification is inadequate for the reliable identification and dissection of the tiny vessels of the spermatic cord, as most of the overlooked veins were adhered to the preserved testicular artery.

Microsurgical transverse 2-suture intussusception vasoepididymostomy: effectiveness and rationality.

BACKGROUND: 2-Suture longitudinal vasoepididymostomy shows superiority to transverse technique in an animal study; to date, this has not been consistently confirmed in human body. In the present study, we evaluated the effectiveness of 2-suture transverse intussusception vasoepididymostomy and compared the rationality between transverse and longitudinal techniques. METHODS: From May 2007 to December 2008, we performed 2-suture transverse vasoepididymostomy in 19 consecutive patients, as described by Marmar with modification. Between March 2009 and January 2010, the internal diameter of the vas lumen and the outer diameter of the epididymal tube were measured using microruler (21 patients and 37 sides). RESULTS: Three patients lost to follow-up. At the first follow-up period (ranged from 10 to 24 months), the patency rate was 56.3% (9/16) and the natural pregnancy rate was 25% (4/16). At the second follow-up period (ranged from 46 to 63 months), the patency rate was 68.8% (11/16), the natural pregnancy rate was 37.5% (6/16), respectively, and the take-home baby rate was 31.3% (5/16). The diameter of the vas lumen and the outer diameter of the epididymal tubule were (0.512 ± 0.046) mm and (0.572 ± 0.051) mm (P < 0.001), respectively. CONCLUSION: Transverse 2-suture intussusception vasoepididymostomy is still an effective technique in treating obstructive azoospermia.

[Insulin-like growth factor-1 gene therapy improves the levels of mRNA and protein of endothelial nitric oxide synthase in aging related erectile dysfunction in rats].

OBJECTIVE: To explore the effects of gene transfer of insulin like growth factor-1 (IGF-1) on the penis of senile rats and the altered levels of mRNA and protein of endothelial nitric oxide synthase (eNOS). METHODS: Ten young (4 months) and 20 senile (24 months) Sprague-Dawley male rats were selected. The senile rats were divided into 2 groups: phosphate buffer solution (PBS)-only (n = 10) and 100 µg IGF-1 plasmid treatment group (n = 10). After a 4-week injection of IGF-1, the responses of intracavernous pressure (ICP) with electrical stimulation to the cavernous nerve and systemic mean arterial pressure (MAP) were evaluated. In the control and transfected senile rats, the levels of eNOS mRNA and protein were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. RESULTS: The ICP/MAP and total ICP were significantly higher in the young control group versus the PBS-only group at Week 4 (P < 0.05). The ICP/MAP and total ICP were significantly higher in the young control group and the 100 µg IGF-1 treatment group versus the PBS-only group at Week 4 (P < 0.05). The levels of mRNA and protein of eNOS were higher in the 100 µg IGF-1 treatment group versus the PBS-only group at Week 4 (0.62 ± 0.16 vs 0.25 ± 0.08, 0.71 ± 0.19 vs 0.27 ± 0.09, both P < 0.05, respectively). CONCLUSION: The gene therapy of IGF-1 can ameliorate erectile functions and improve the levels of mRNA and protein of eNOS in senile rats.

Higher expression of mRNA and protein of insulin-like growth factor binding protein-3 in old rat penile tissues: implications for erectile dysfunction.

INTRODUCTION: Previous studies have confirmed the gene transfer of insulin-like growth factor-1 (IGF-1) and the IGF-1 protein can improve the erectile function in aging rats. IGF binding protein (BP)-3 can regulates the availability of IGF-I. The higher expression of IGFBP-3 may play an important role in erectile dysfunction (ED). AIM: The study aimed to investigate the mRNA and protein expression of IGFBP-3 in young and old rat penile tissues and assess the alteration of the penile structure and the NO-guanosine 3',5'-cyclic-monophosphate (cGMP) signaling pathways-related marker in ED associated with aging. MAIN OUTCOME MEASURES: The main outcome measures for this study were the expression of IGFBP-3, morphological changes, NO-cGMP signaling pathways-related marker, erectile responses were determined. METHODS: Traditional reverse transcriptase polymerase chain reaction (RT-PCR) and real-time PCR were performed to examine the mRNA expression of the IGFBP-3. The Western blot was used to confirm the protein expression. Immunohistochemistry was also performed to identify the cellular localization of the encoded protein. The percentage of smooth muscle in corpus cavernosum tissue, the activity of nitric oxide synthase (NOS), and concentration of cGMP in penile tissue were also analyzed. RESULTS: The expression levels of IGFBP-3 of mRNA and protein were greatly increased in aging rats compared with young control rats, which is confirmed by traditional RT-PCR, real-time PCR, and Western blot (P < 0.01, respectively). Increased IGFBP-3 protein was localized to the epithelium of the urethra, penile endothelium, and smooth muscle in the corpus cavernosum. Significant depletion of the smooth muscle density relative to the connective tissue was also observed in the penis of the aged rats, and the lower activity of NOS and lower concentration of cGMP was also demonstrated accompanied with a significant reduction in the intracavernous pressure. CONCLUSIONS: Our data suggest that the increased mRNA and protein expression of IGFBP-3 in old rats may play a role in ED.

Effects of plant extract neferine on cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in rabbit corpus cavernosum in vitro.

AIM: To further investigate the relaxation mechanism of neferine (Nef), a bis-benzylisoquinoline alkaloid extracted (isolated) from the green seed embryo of Nelumbo nucifera Gaertn in China, on rabbit corpus cavernosum tissue in vitro. METHODS: The effects of Nef on the concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in isolated and incubated rabbit corpus cavernosum tissue were recorded using 125I radioimmunoassay. RESULTS: The basal concentration of cAMP in corpus cavernosum tissue was 5.67 +/- 0.97 pmol/mg. Nef increased the cAMP concentration in a dose-dependent manner (P < 0.05), but this effect was not inhibited by an adenylate cyclase inhibitor (cis-N-[2-phenylcyclopentyl]azacyclotridec-1-en-2-amine, MDL-12, 330A) (P > 0.05). The accumulation of cAMP induced by prostaglandin E1 (PGE1, a stimulator of cAMP production) was also augmented by Nef in a dose-dependent manner (P < 0.05). The basal concentration of cGMP in corpus cavernosum tissue is 0.44 +/- 0.09 pmol/mg. Nef did not affect this concentration of cGMP, either in the presence or in the absence of a guanyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) (P > 0.05). Also, sodium nitroprusside (SNP, a stimulator of cGMP production)-induced cGMP production was not enhanced by Nef (P > 0.05). CONCLUSION: Nef, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting phosphodiesterase activity.

[Etiology and individualized treatment of erectile dysfunction in young adult men: a report of 110 cases].

OBJECTIVE: To investigate the etiology and individualized treatment of erectile dysfunction (ED) in young adult men. METHODS: Included in the investigation were 110 young adult men with ED, at the mean age of 28 (ranging from 22 to 39) and with the average disease course of 24 months (ranging from 6 to 48). The etiology of ED was determined for each patient by history inquiry, medical examination, laboratory investigation and erectile function test, and then individualized therapies were administered accordingly. RESULTS: Of all the diagnosed cases of ED, 42 (38.2%) were psychogenic, 36 (32.7%) organic and 32 (29.1%) of the mixed type. Four cases of schizophrenia were transferred elsewhere, 4 pelvic fracture induced cases gave up treatment, and the other 102 received individualized therapies, with the average effectiveness rate of 88.2%. CONCLUSION: Determination of the etiology of ED and the corresponding individualized treatment is the linchpin for improving the therapeutic effect of ED in young adult men.

[Effects of senility on inducible nitric oxide synthase expression and cell apoptosis in rat penis].

OBJECTIVES: To investigate the effect of senility on inducible nitric oxide synthase (iNOS) expression and apoptosis in rat penis. METHODS: The rats were divided into three groups randomly: senescent, aged and young. Their penises were harvested to detect iNOS expression by immunohistochemistry and cell apoptosis rate by TUNEL, respectively. RESULTS: iNOS expression were 0.24 +/- 0.03, 0.17 +/- 0.02, 0.12 +/- 0.03 (relative A) and cell apoptosis rate were (1.41 +/- 0.78)%, (0.94 +/- 0.43)% and (0.50 +/- 0.23 )%, respectively, in the tissues of three groups. The differences among three groups were considerable significance (P <0.05). CONCLUSION: It maybe one of the mechanisms of erectile dysfunction in the aging male that senility causes the increase of iNOS expression and cell apoptosis.

[The relaxation effects of six extracts from Chinese herbs on the corpus cavernosum tissue of rabbit in vitro].

OBJECTIVE: To study the relaxants effects of six extractions from Chinese Herbs (neferine, tetrandrine, kakonein, scutellarin, ginsenoside Rgl and ginsenoside Rb1) on the corpus cavernosum tissue of rabbit in vitro. METHODS: Isolated stripes of rabbit corpus cavernosum tissue were precontracted with 10(-5) mol/L phenylephrine (PE). Relaxation in response to cumulative doses of six extracts at (10(-8) - 10(-3)) mol/L was determined. RESULTS: On rabbit cavernosal muscle stripes precontracted with PE, neferine, tetrandrine, kakonein and scutellarin showed dose dependent relaxation. IC50 values were 4.60 x 10(-6), 3.73 x 10(-5), 8.03 x 10(-4) and 3.33 x 10(-3) mol/L, respectively. However, in the meantime, it was found that the relaxant effects of ginsenoside Rgl and ginsenoside Rbl less significant to stripes precontracted with PE. When the final concentration was 10(-3) mol/L, the relaxations were only (16.32 +/- 5.45)% and (11.21 +/- 3.10)%. CONCLUSION: Among the six extracts which showed relaxant effects to rabbit cavernosal muscle stripes precontracted with PE, neferine had greater functions than the other five extracts.

[Expression of the kallikreins-kinins system in the corpus cavernosum of rats].

OBJECTIVE: To study the expression of the kallikreins-kinins system in the corpus cavernosum of rats. METHODS: The expression of tissue kallikrein I and kinin B2 receptor gene in the corpus cavernosum and heart of adult rats was detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The tissue kallikrein I and kinin B2 receptor were detected in the corpus cavernosum as well as in the heart of the rats and the contents were similar. CONCLUSION: A kallikreins-kinins system exists in the corpus cavernosum of rats, and the content is rich, almost similar to that in the heart.

[Effects of tetramethylpyrazine on cytosolic free calcium concentration in penis corpus cavernsum smooth muscle cells in rabbits].

OBJECTIVE: To study the effects of Chinese medicine tetramethylpyrazine (TMP) on intracellular free calcium ([Ca2+]i) in cultured penis corpus cavernosum smooth muscle cell (PCSMC) in rabbits. METHODS: By using laser scanning confocal microscope (LSCM), the [Ca2+]i fluorescence signal changes was investigated in cultured PCSMC loaded with Ca2+ indicator Fluo-3/AM and divided into potassium chloride(KCl) group and norepinephrine (NE) group. Compared with verapamil (Ver), the effects of TMP was observed in different concentrations on [Ca2+]i increase induced by high potassium and NE. RESULTS: TMP had no obvious effect on resting PCSMC [Ca2+]i. It was found that 1, 10, 100 mumol/L TMP significantly inhibited [Ca2+]i increase induced by high potassium-depolarization. The peak inhibition rates were (38.6 +/- 3.0)%, (44.1 +/- 2.4)% and (53.7 +/- 4.1)% respectively. TMP could also inhibit cytosolic calcium pool release induced by 1 mumol/L NE. The peak inhibition rates were (13.9 +/- 2.7)%, (21.2 +/- 1.9)% and (29.5 +/- 3.6)% respectively. CONCLUSIONS: TMP can inhibit rabbit PCSMC [Ca2+]i significantly by suppressing voltage-dependent calcium channel and cytosolic calcium pool release. The effect, similar to Ver, signifies the important mechanism of erectile dysfunction (ED) therapy.

[The relaxation effects of tetrandrine on the corpus cavernosum tissue of rabbit in vitro].

OBJECTIVES: To study the relaxation effects of tetrandrine on the corpus cavernosum tissue of rabbit in vitro. METHODS: 1. The fluctuation of the dose-response relaxation curves for the contraction of KCl induced by tetrandrine was observed with isolated rabbit corpus cavernosum tissue. 2. Isolated strips of rabbit corpus cavernosum tissue were precontracted with 10 mumol/L phenylephrine(PE). Relaxation in response to cumulative doses of tetrandrine was determined in the absence and presence of nitric oxide synthase inhibitor (L-NNA) and soluble guanylate cyclase inhibitor (methylthioninium). RESULTS: 1. The dose-response curves of KCl were shifted to the right nonparallelly, and the maximal responses were depressed to (73.0 +/- 3.8)% and (41.5 +/- 3.4)%, respectively, in the presence of tetrandrine(10 mumol/L, 30 mumol/L). 2. On rabbit cavernosal muscle stripes precontracted with PE(10 mumol/L), increasing concentrations of tetrandrine (1 mumol/L, 10 mumol/L, 30 mumol/L and 100 mumol/L) showed dose dependent relaxation [(6.0 +/- 1.4)%, (21.3 +/- 2.2)%, (47.4 +/- 3.3)%, and (68.1 +/- 3.6)%, P < 0.01]. However, in the meantime, it was found that these relaxation effects were not affected by the presence of L-NNA and methylthioninium (P > 0.05). CONCLUSIONS: Tetrandrine was effective in relaxing rabbit corpus cavernosum tissue in vitro in a dose-dependent style. The mechanism might be related with its blocking effect on calcium channel, but not the NO-cGMP passage.

[Advance in calcium channel blockers relaxing corpus cavernosum smooth muscle].

Calcium channels exist extensively in the membrane of cardiac, skeletal, smooth muscle cell and neuron. Calcium channel blockers (CCB) were widely used for the treatment of cardiovascular diseases because they could relax vascular smooth muscle. Experimental researches on calcium channel blockers relaxing corpus cavernosum smooth muscle have been reported recently. Whether the blockers can be used for the clinical diagnosis and treatment of erectile dysfunction still need to be further investigated.