RESUMO
SUMMARY: Previous studies from our group described the consequences of using ethanol on penile erection. Nevertheless, the molecular mechanisms surrounding microRNAs, apoptosis process and their relationship with erectile dysfunction associated with alcohol consumption are still poorly understood. The objective of this analysis was to evaluate the mechanism of apoptosis by the expression of AIF and PARP, as well as their regulatory microRNAs: miR-145, miR-210 and miR-486, in the corpus cavernosum of rats submitted to a semivoluntary alcoholism model. For this study 24 Wistar rats were divided into two groups: control (C) and treated with 20 % ethanol (A) for seven weeks. The corpus cavernosum samples were prepared for immunohistochemical analysis of AIF and PARP protein expression, and microRNAs miR-145, miR-210, miR-486 gene expression in cavernous tissue was performed by real time PCR. The immunohistochemical analysis showed little nuclear positive labeling for the protein PARP and AIF in the corpus cavernosum of control and ethanol treated animals. After analysis of miR-145, -210 and -486 microRNA expression in the 12 animals studied, no results were found with significant statistical difference between the control and alcoholized groups. The expression of AIF and PARP and their regulatory microRNAs involved in apoptotic process (miR-145, miR-210 and miR-486) were not altered in the corpus cavernosum of rats submitted to semivoluntary alcoholism.
RESUMEN: Estudios previos de nuestro grupo describieron las consecuencias del uso de etanol en la erección del pene. Sin embargo, los mecanismos moleculares que rodean a los microARN, el proceso de apoptosis y su relación con la disfunción eréctil asociada con el consumo de alcohol aún no se conocen bien. El objetivo de este análisis fue evaluar el mecanismo de apoptosis mediante la expresión de AIF y PARP, así como sus microARN reguladores: miR-145, miR-210 y miR-486, en el cuerpo cavernoso de ratas sometidas a un modelo de alcoholismo semivoluntario. Se dividieron 24 ratas Wistar en dos grupos: control (C) grupo de ratas tratadas con etanol al 20 % (A) durante siete semanas. Las muestras del cuerpo cavernoso se prepararon para el análisis inmunohistoquímico de la expresión de la proteína AIF y PARP, y la expresión del gen microRNAs miR-145, miR-210, miR-486 en tejido cavernoso se realizó por PCR en tiempo real. El análisis inmunohistoquímico mostró escaso etiquetado nuclear positivo para la proteína PARP y AIF en el cuerpo cavernoso de los animales de control y tratados con etanol. Después del análisis de la expresión de microARN miR-145, -210 y -486 no se encontraron resultados con diferencias estadísticas significativas entre los grupos control y alcoholizados. La expresión de AIF y PARP y sus microARN reguladores involucrados en el proceso apoptótico (miR-145, miR-210 y miR-486) no se alteraron en el cuerpo cavernoso de las ratas sometidas a alcoholismo semivoluntario.
Assuntos
Animais , Ratos , Apoptose , Alcoolismo/metabolismo , Disfunção Erétil/metabolismo , Pênis/fisiopatologia , Pênis/química , Imuno-Histoquímica , Ratos Wistar , MicroRNAs/análise , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Animais de Doenças , Alcoolismo/fisiopatologia , Fator de Indução de Apoptose/análise , Fator de Indução de Apoptose/genética , Fator de Indução de Apoptose/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Disfunção Erétil/fisiopatologiaRESUMO
INTRODUCTION: The macroscopic dynamic of fetal penis development presents a pattern resembling the unfolding of a spiral, so congenital ventral penile curvature could indicate that this natural sequence has been interrupted. Our aim in this article is to offer a mathematical model of congenital ventral curvature of the penis. MATERIALS AND METHODS: Five individuals who presented with congenital ventral penile curvature and three who presented with acquired penile ventral curvature due to Peyronie's disease were evaluated. The penises were photographed during an induced erection test and the penile curvature patterns were compared with an equiangular spiral. When an association was found, a potential relationship to the golden spiral-a type of equiangular spiral-was also assessed. The mathematical spiral relationships were analyzed using Wolfram CDF Player® (Logarithmic Spiral) and PhiMatrix® software. The Wolfram software generated logarithmic spirals equivalent to the penile curvature with appropriate mathematical values. The PhiMatrix software, which builds any golden spirals from golden rectangles, was used to check whether the spiral was golden as well as equiangular. RESULTS: An equiangular spiral that was also golden was found in all cases of congenital ventral penile curvature. In contrast, none of the acquired penile ventral curvature cases showed a specific pattern. CONCLUSION: Congenital ventral penile curvature has the mathematical pattern of a golden spiral. Our results offer a mathematical algorithm for potential use in surgical reconstruction procedures, regenerative medicine, tissue engineering, robotics, and body-machine interfaces.
Assuntos
Ereção Peniana/fisiologia , Induração Peniana/fisiopatologia , Pênis/fisiopatologia , Adolescente , Idoso , Criança , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Modelos TeóricosRESUMO
INTRODUCTION: Priapism is the persistent and painful erection of the penis and is a common sickle cell disease (SCD) complication. AIM: The goal of this study was to characterize clinical and genetic factors associated with priapism within a large multi-center SCD cohort in Brazil. METHODS: Cases with priapism were compared to SCD type-matched controls within defined age strata to identify clinical outcomes associated with priapism. Whole blood single nucleotide polymorphism genotyping was performed using a customized array, and a genome-wide association study (GWAS) was conducted to identify single nucleotide polymorphisms associated with priapism. MAIN OUTCOME MEASURE: Of the 1,314 male patients in the cohort, 188 experienced priapism (14.3%). RESULTS: Priapism was more common among older patients (P = .006) and more severe SCD genotypes such as homozygous SS (P < .0001). In the genotype- and age-matched analyses, associations with priapism were found for pulmonary hypertension (P = .05) and avascular necrosis (P = .01). The GWAS suggested replication of a previously reported candidate gene association of priapism for the gene transforming growth factor beta receptor 3 (TGFBR3) (P = 2 × 10-4). CLINICAL IMPLICATIONS: Older patients with more severe genotypes are at higher risk of priapism, and there is a lack of consensus on standard treatment strategies for priapism in SCD. STRENGTHS & LIMITATIONS: This study characterizes SCD patients with any history of priapism from a large multi-center cohort. Replication of the GWAS in an independent cohort is required to validate the results. CONCLUSION: These findings extend the understanding of risk factors associated with priapism in SCD and identify genetic markers to be investigated in future studies to further elucidate priapism pathophysiology. Ozahata M, Page GP, Guo Y, et al. Clinical and Genetic Predictors of Priapism in Sickle Cell Disease: Results from the Recipient Epidemiology and Donor Evaluation Study III Brazil Cohort Study. J Sex Med 2019;16:1988-1999.
Assuntos
Anemia Falciforme/complicações , Pênis/fisiopatologia , Priapismo/diagnóstico , Adulto , Brasil , Estudos de Coortes , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/fisiologia , Polimorfismo de Nucleotídeo Único , Priapismo/etiologia , Fatores de RiscoRESUMO
ABSTRACT Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.
Assuntos
Humanos , Animais , Masculino , Idoso , Pênis/efeitos dos fármacos , Acroleína/análogos & derivados , Óleos Voláteis/farmacologia , Cinnamomum zeylanicum/química , Relaxamento Muscular/efeitos dos fármacos , Pênis/fisiopatologia , Fenilefrina/farmacologia , Vasoconstritores/farmacologia , Acroleína/farmacologia , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Reprodutibilidade dos Testes , Análise de Variância , Ratos Sprague-Dawley , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia , Disfunção Erétil/fisiopatologia , Disfunção Erétil/tratamento farmacológico , Pessoa de Meia-Idade , Relaxamento Muscular/fisiologiaRESUMO
Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.
Assuntos
Acroleína/análogos & derivados , Cinnamomum zeylanicum/química , Relaxamento Muscular/efeitos dos fármacos , Óleos Voláteis/farmacologia , Pênis/efeitos dos fármacos , Acroleína/farmacologia , Idoso , Análise de Variância , Animais , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Relaxamento Muscular/fisiologia , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Pênis/fisiopatologia , Fenilefrina/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Citrato de Sildenafila/farmacologia , Vasoconstritores/farmacologiaRESUMO
Erectile dysfunction is a common condition that affects men over age 40. It is highly related to obesity. The corpus cavernosum is the most important structure involved in erection. The aim of this study was to evaluate the structure of the corpus cavernosum of mice fed with a high energy density diet (HED). At 3 months of age, male C57BL/6 mice were fed with a HED diet (50% lipids) or standard chow (SC) diet (10% lipids) for 14 weeks. Afterwards, the animals were euthanized and the corpus cavernosum was analyzed through stereology. Statistical significance was calculated by the student's t-test (p < 0.05). The group fed with HED diet showed higher values of body weight, blood pressure and higher rates of cholesterol, triglycerides, and glucose from the second week to the end of the experiment. The HED group showed a significant increase in the connective tissue (15%) and a decrease in smooth muscle fibers (41%). The testosterone concentration in the HED group was 63% lower than in SC animals. Animals fed with a HED presented reduced testosterone serum levels and morphological changes on the corpus cavernosum, which may be related to erectile dysfunction.
Assuntos
Gorduras na Dieta/efeitos adversos , Miócitos de Músculo Liso/patologia , Pênis/patologia , Testosterona/sangue , Animais , Modelos Animais de Doenças , Disfunção Erétil/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/fisiopatologia , Pênis/fisiopatologiaRESUMO
OBJECTIVES: To study the efficacy of Low intensity Extracorporeal Shockwave Therapy (Li- ESWT) for the treatment of erectile dysfunction (ED) in kidney transplanted men. METHODS: Twenty men (mean age = 53.7 years) were selected. This was a double-blinded, prospective, randomized, sham-controlled trial. The ESWT protocol was based in a 2 treatment sessions per week for 3 weeks. The sham treatment was performed using the same device replacing the effective probe for one that emits zero energy. Baseline and follow-up assessment was performed with International Index of Erectile Function Questionnaire (IIEF) score and Erection Hardness Score (EHS) after 1, 4 and 12 months. Penile Doppler was performed before and after treatment. RESULTS: A total of 20 patients were recruited, 10 patients in each group. Baseline scores were similar. The mean EHS in after 1 month were 2.5 ± 0.85 (Li-EWST) and 2.4 ± 0.7 (Sham therapy), p = 0.724 . After 4 months it was 2.4 ± 0.7 and 2.6 ± 0.84, p = 0,0004 (between the moments) . The baseline IIEF score was 14.9 ± 3(Sham Theraphy) and 10.9 ± 5.1 (Li-EWST). The mean IIEF score after 1 month was 15.6 ± 6.1 (Li-EWST) and 16.6 ± 5.4 (Sham therapy). The mean IIEF score after 4 months was 17.2 ± 5.7 (Li-EWST) and 16.5 ± 5 (Sham therapy), p < 0.0001 (between the moments). IIEF score improvement was higher than 5 in 70% (ranged from 0-10) and in 10% (ranged from 1-14) in Li-ESWT and Sham groups, respectively. The mean change in IIEF score after 12 months was 4.8 in Li-ESWT group .Penile Doppler parameters were similar between groups and did not present improvements. CONCLUSIONS: Li-ESWT is a treatment with clinical efficacy. Despite evidences suggesting neoagiogenesis, our short protocol had no impact in penile Doppler parameters.
Assuntos
Disfunção Erétil/terapia , Transplante de Rim , Pênis/fisiopatologia , Terapia por Ultrassom , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana , Pênis/diagnóstico por imagem , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Ultrassonografia DopplerRESUMO
ABSTRACT Objectives: Evaluate the demographic data, etiology, operative findings and results of surgical treatment of penile fracture (PF) in men who have sex with men(MSM) with emphasis on sexual complications. Materials and Methods: We studied 216 patients underwent surgical correction of PF at our hospital. Patients self-identified as MSM were followed for at least 6 months. Demographic data, presentation, operative findings, International Index of Erection Function - 5 (IIEF-5) and the Premature Ejaculation Diagnostic Tool. Results: Of 216 PF cases, 4 (1.8%) were MSM. All cases resulted from sexual activity and all patients reported using the "doggy style" position during anal intercourse. Unilateral or bilateral injury of corpus cavernosum was found in 2 patients each. One (25%) patient had complete urethral injury associated with bilateral corpus cavernosum lesion. During the follow-up period, all patients developed some type of sexual complication. One patient reported penile pain during intercourse. Another patient experienced low sexual desire and premature ejaculation. This patient was also dissatisfied with the aesthetic result of the surgical scar and complained about decreased penis size after surgery. The third case developed delayed ejaculation. The fourth patient experienced mild to moderate erectile dysfunction. This same patient presented with penile curvature. Finally, palpable fibrotic nodules in the operative area were observed in all cases. Conclusions: Sexual activity in the "doggy style" position was the commonest cause of PF in MSM. Sexual dysfunction is always present in gay man after surgery for PF. However, additional studies with larger samples should be coinducted.
Assuntos
Humanos , Masculino , Adulto , Pênis/lesões , Disfunções Sexuais Fisiológicas/etiologia , Homossexualidade Masculina , Pênis/fisiopatologia , Postura , Ruptura/cirurgia , Ruptura/complicações , Ruptura/fisiopatologia , Comportamento Sexual , Disfunções Sexuais Fisiológicas , Ereção Peniana/fisiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Pessoa de Meia-IdadeRESUMO
ABSTRACT Introduction: The study was aimed to assess the presence of actual differences between the objective and the perceived magnitude of a curvature between patients affected by Peyronie's disease (PD) and congenital penile curvature (CPC). Materials and Methods: Wee analysed a cohort of 88 consecutive patients seeking medi- cal help for either CPC or PD. All patients were invited to provide a self-made drawing of their penis in erection in order to obtain self-provided description of the deformity. An objective measurement of the deformity was also performed drawing two intersecting lines through the center of the distal and proximal straight section of the penile shaft. Results: Our findings showed significant differences between patient self-estimation and the objective measurements of the penile angulation performed by trained experts, with only 32% of patients correctly assessing their own curvature. Overall, patients tended to overestimate (56%) their degree of curvature, but the results are different in patients with PD than those with CPC. In the 60 men (68%) who did not accurately assess their curvature, PD patients generally overestimated their curvature versus CPC patients (67% vs 16%). On the contrary CPC patients underestimated their curvature compared to PD (42% vs. 4%). Conclusion: In order to improve patients' satisfaction rates, the surgeon needs to take into consideration the patient's perception of the deformity when planning the type of surgical correction.
Assuntos
Humanos , Masculino , Adolescente , Adulto , Idoso , Adulto Jovem , Induração Peniana/patologia , Pênis/anormalidades , Pênis/patologia , Autoavaliação Diagnóstica , Induração Peniana/fisiopatologia , Induração Peniana/psicologia , Pênis/fisiopatologia , Percepção , Valores de Referência , Índice de Gravidade de Doença , Ereção Peniana/fisiologia , Análise Multivariada , Pessoa de Meia-IdadeRESUMO
Recent evidence shows that chronic ethanol consumption increases endothelin (ET)-1 induced sustained contraction of trabecular smooth muscle cells of the corpora cavernosa in corpus cavernosum of rats by a mechanism that involves increased expression of ETA and ETB receptors. Our goal was to evaluate the effects of alcohol and diabetes and their relationship to miRNA-155, miRNA-199 and endothelin receptors in the corpus cavernosum and blood of rats submitted to the experimental model of diabetes mellitus and chronic alcoholism. Forty-eight male Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D), and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study the protein expression of endothelin receptors by immunohistochemistry and expression of miRNAs-155 and -199 in serum and the cavernous tissue. Immunostaining for endothelin receptors was markedly higher in the A, D, and AD groups than in the C group. Moreover, a significant hypoexpression of the miRNA-199 in the corpus cavernosum tissue from the AD group was observed, compared to the C group. When analyzing the microRNA profile in blood, a significant hypoexpression of miRNA-155 in the AD group was observed compared to the C group. The miRNA-199 analysis demonstrated significant hypoexpression in D and AD groups compared to the C group. Our findings in corpus cavernosum showed downregulated miRNA-155 and miRNA-199 levels associated with upregulated protein expression and unaltered mRNA expression of ET receptors suggesting decreased ET receptor turnover, which can contribute to erectile dysfunction in diabetic rats exposed to high alcohol levels.
Assuntos
Alcoolismo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Endotelina-1/análise , MicroRNAs/análise , Pênis/metabolismo , Receptor de Endotelina A/análise , Receptor de Endotelina B/análise , Alcoolismo/complicações , Alcoolismo/fisiopatologia , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Imuno-Histoquímica , Masculino , Pênis/fisiopatologia , Ratos , Ratos WistarRESUMO
INTRODUCTION: The study was aimed to assess the presence of actual differences between the objective and the perceived magnitude of a curvature between patients affected by Peyronie's disease (PD) and congenital penile curvature (CPC). MATERIALS AND METHODS: Wee analysed a cohort of 88 consecutive patients seeking medical help for either CPC or PD. All patients were invited to provide a self-made drawing of their penis in erection in order to obtain self-provided description of the deformity. An objective measurement of the deformity was also performed drawing two intersecting lines through the center of the distal and proximal straight section of the penile shaft. RESULTS: Our findings showed significant differences between patient self-estimation and the objective measurements of the penile angulation performed by trained experts, with only 32% of patients correctly assessing their own curvature. Overall, patients tended to overestimate (56%) their degree of curvature, but the results are different in patients with PD than those with CPC. In the 60 men (68%) who did not accurately assess their curvature, PD patients generally overestimated their curvature versus CPC patients (67% vs 16%). On the contrary CPC patients underestimated their curvature compared to PD (42% vs. 4%). CONCLUSION: In order to improve patients' satisfaction rates, the surgeon needs to take into consideration the patient's perception of the deformity when planning the type of surgical correction.
Assuntos
Autoavaliação Diagnóstica , Induração Peniana/patologia , Pênis/anormalidades , Pênis/patologia , Adolescente , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ereção Peniana/fisiologia , Induração Peniana/fisiopatologia , Induração Peniana/psicologia , Pênis/fisiopatologia , Percepção , Valores de Referência , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVES: Evaluate the demographic data, etiology, operative findings and results of surgical treatment of penile fracture (PF) in men who have sex with men(MSM) with emphasis on sexual complications. MATERIALS AND METHODS: We studied 216 patients underwent surgical correction of PF at our hospital. Patients self-identified as MSM were followed for at least 6 months. Demographic data, presentation, operative findings, International Index of Erection Function - 5 (IIEF-5) and the Premature Ejaculation Diagnostic Tool. RESULTS: Of 216 PF cases, 4 (1.8%) were MSM. All cases resulted from sexual activity and all patients reported using the "doggy style" position during anal intercourse. Unilateral or bilateral injury of corpus cavernosum was found in 2 patients each. One (25%) patient had complete urethral injury associated with bilateral corpus cavernosum lesion. During the follow-up period, all patients developed some type of sexual complication. One patient reported penile pain during intercourse. Another patient experienced low sexual desire and premature ejaculation. This patient was also dissatisfied with the aesthetic result of the surgical scar and complained about decreased penis size after surgery. The third case developed delayed ejaculation. The fourth patient experienced mild to moderate erectile dysfunction. This same patient presented with penile curvature. Finally, palpable fibrotic nodules in the operative area were observed in all cases. CONCLUSIONS: Sexual activity in the "doggy style" position was the commonest cause of PF in MSM. Sexual dysfunction is always present in gay man after surgery for PF. However, additional studies with larger samples should be coinducted.
Assuntos
Homossexualidade Masculina , Pênis/lesões , Disfunções Sexuais Fisiológicas/etiologia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/fisiologia , Pênis/fisiopatologia , Postura , Estudos Retrospectivos , Fatores de Risco , Ruptura/complicações , Ruptura/fisiopatologia , Ruptura/cirurgia , Comportamento Sexual , Disfunções Sexuais Fisiológicas/fisiopatologia , Resultado do TratamentoRESUMO
Recent evidence shows that chronic ethanol consumption increases endothelin (ET)-1 induced sustained contraction of trabecular smooth muscle cells of the corpora cavernosa in corpus cavernosum of rats by a mechanism that involves increased expression of ETA and ETB receptors. Our goal was to evaluate the effects of alcohol and diabetes and their relationship to miRNA-155, miRNA-199 and endothelin receptors in the corpus cavernosum and blood of rats submitted to the experimental model of diabetes mellitus and chronic alcoholism. Forty-eight male Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D), and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study the protein expression of endothelin receptors by immunohistochemistry and expression of miRNAs-155 and -199 in serum and the cavernous tissue. Immunostaining for endothelin receptors was markedly higher in the A, D, and AD groups than in the C group. Moreover, a significant hypoexpression of the miRNA-199 in the corpus cavernosum tissue from the AD group was observed, compared to the C group. When analyzing the microRNA profile in blood, a significant hypoexpression of miRNA-155 in the AD group was observed compared to the C group. The miRNA-199 analysis demonstrated significant hypoexpression in D and AD groups compared to the C group. Our findings in corpus cavernosum showed downregulated miRNA-155 and miRNA-199 levels associated with upregulated protein expression and unaltered mRNA expression of ET receptors suggesting decreased ET receptor turnover, which can contribute to erectile dysfunction in diabetic rats exposed to high alcohol levels.
Assuntos
Animais , Masculino , Ratos , Alcoolismo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Endotelina-1/análise , MicroRNAs/análise , Pênis/metabolismo , Receptor de Endotelina A/análise , Receptor de Endotelina B/análise , Alcoolismo/complicações , Alcoolismo/fisiopatologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Imuno-Histoquímica , Pênis/fisiopatologia , Ratos WistarRESUMO
ABSTRACT Objective Diabetes affects the erectile function significantly. However, the penile alterations in the early stage of diabetes in experimental animal models have not been well studied. We examined the changes of the penis and its main erectile components in diabetic rats. Materials and methods Male Sprague-Dawley rats were divided into 2 groups: streptozotocin (STZ)-induced diabetics and age-matched controls. Three or nine weeks after diabetes induction, the penis was removed for immunohistochemical staining of smooth muscle and neuronal nitric oxide synthase (nNOS) in midshaft penile tissues. The cross-sectional areas of the whole midshaft penis and the corpora cavernosa were quantified. The smooth muscle in the corpora cavernosa and nNOS in the dorsal nerves were quantified. Results The weight, but not the length, of the penis was lower in diabetics. The cross-sectional areas of the total midshaft penis and the corpora cavernosa were lower in diabetic rats compared with controls 9 weeks, but not 3 weeks after diabetes induction. The cross-sectional area of smooth muscle in the corpora cavernosa as percentage of the overall area of the corpora cavernosa was lower in diabetic rats than in controls 9 weeks, but not 3 weeks after diabetes induction. Percentage change of nNOS in dorsal nerves was similar at 3 weeks, and has a decreased trend at 9 weeks in diabetic rats compared with controls. Conclusions Diabetes causes temporal alterations in the penis, and the significant changes in STZ rat model begin 3-9 weeks after induction. Further studies on the reversibility of the observed changes are warranted.
Assuntos
Animais , Masculino , Ratos , Pênis/fisiopatologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Disfunção Erétil/etiologia , Músculo Liso/fisiopatologia , Pênis/inervação , Ratos Sprague-Dawley , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Óxido Nítrico Sintase Tipo I/metabolismo , Disfunção Erétil/fisiopatologiaRESUMO
OBJECTIVE: To test the hypothesis that naive Wistar audiogenic rats (WARs) display erectile dysfunction (ED), which is associated with increased sympathetic-mediated contractile tone and decreased nitric oxide-mediated relaxation responses of the cavernous tissue. METHODS: Changes in the ratio of the maximal intracavernosal pressure-mean arterial pressure after the electrical stimulation of the right major pelvic ganglion were determined in vivo. Cavernosal contractility was induced by electrical field stimulation and phenylephrine. In addition, nonadrenergic-noncholinergic (NANC)-induced relaxation was determined. Rho-kinase (ROCK) pathway proteins, neuronal nitric oxide synthase (nNOS) protein expression, and endothelial nitric oxide synthase (eNOS) and extracellular signal-regulated kinase 1/2 activities were determined by Western blot. RESULTS: WARs display a significant decrease in maximal intracavernosal pressure-mean arterial pressure responses suggesting ED in this strain. Sympathetic-mediated contractile responses were increased in WARs and contractile responses to phenylephrine were not changed. The increased sympathetic-mediated contractile responses were not associated with changes in the ROCK pathway. On the other hand, NANC-mediated relaxation responses were significantly reduced in WARs. This functional response was accompanied by decreased nNOS and total eNOS protein expressions, augmented phosphorylated eNOS, and decreased extracellular signal-regulated kinase 1/2 phosphorylation levels. CONCLUSION: Our data have demonstrated that naive WARs display ED in vivo that is associated with increased sympathetic-mediated contractile responses and decreased NANC-mediated relaxation responses. The increase in contractile responses is independent of the ROCK pathway, and the changes in relaxation responses are associated with a decrease in nNOS protein expression, which may activate compensatory mechanisms in the cavernous tissue.
Assuntos
Epilepsia Reflexa/complicações , Disfunção Erétil/fisiopatologia , Óxido Nítrico Sintase Tipo I/biossíntese , Ereção Peniana/fisiologia , Pênis/fisiopatologia , Animais , Western Blotting , Modelos Animais de Doenças , Disfunção Erétil/etiologia , Disfunção Erétil/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
Ethanol consumption is associated with an increased risk of erectile dysfunction (ED), but the molecular mechanisms through which ethanol causes ED remain elusive. Reactive oxygen species are described as mediators of ethanol-induced cell toxicity/damage in distinctive tissues. The enzyme NADPH oxidase is the main source of reactive oxygen species in the endothelium and vascular smooth muscle cells and ethanol is described to increase NADPH oxidase activation and reactive oxygen species generation. This study evaluated the contribution of NADPH oxidase-derived reactive oxygen species to ethanol-induced ED, endothelial dysfunction and production of pro-inflammatory and redox-sensitive proteins in the rat cavernosal smooth muscle (CSM). Male Wistar rats were treated with ethanol (20% v/v) or ethanol plus apocynin (30mg/kg/day; p.o. gavage) for six weeks. Apocynin prevented both the decreased in acetylcholine-induced relaxation and intracavernosal pressure induced by ethanol. Ethanol increased superoxide anion (O2-) generation and catalase activity in CSM, and treatment with apocynin prevented these responses. Similarly, apocynin prevented the ethanol-induced decreased of nitrate/nitrite (NOx), hydrogen peroxide (H2O2) and SOD activity. Treatment with ethanol increased p47phox translocation to the membrane as well as the expression of Nox2, COX-1, catalase, iNOS, ICAM-1 and p65. Apocynin prevented the effects of ethanol on protein expression and p47phox translocation. Finally, treatment with ethanol increased both TNF-α production and neutrophil migration in CSM. The major new finding of this study is that NADPH oxidase-derived reactive oxygen species play a role on chronic ethanol consumption-induced ED and endothelial dysfunction in the rat CSM.
Assuntos
Disfunção Erétil/metabolismo , Etanol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , NADPH Oxidases/metabolismo , Pênis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/fisiopatologia , Masculino , Músculo Liso/metabolismo , Músculo Liso/fisiopatologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Pênis/fisiopatologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
OBJECTIVE: Diabetes affects the erectile function significantly. However, the penile alterations in the early stage of diabetes in experimental animal models have not been well studied. We examined the changes of the penis and its main erectile components in diabetic rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 2 groups: streptozotocin (STZ)-induced diabetics and age-matched controls. Three or nine weeks after diabetes induction, the penis was removed for immunohistochemical staining of smooth muscle and neuronal nitric oxide synthase (nNOS) in midshaft penile tissues. The cross-sectional areas of the whole midshaft penis and the corpora cavernosa were quantified. The smooth muscle in the corpora cavernosa and nNOS in the dorsal nerves were quantified. RESULTS: The weight, but not the length, of the penis was lower in diabetics. The crosssectional areas of the total midshaft penis and the corpora cavernosa were lower in diabetic rats compared with controls 9 weeks, but not 3 weeks after diabetes induction. The cross-sectional area of smooth muscle in the corpora cavernosa as percentage of the overall area of the corpora cavernosa was lower in diabetic rats than in controls 9 weeks, but not 3 weeks after diabetes induction. Percentage change of nNOS in dorsal nerves was similar at 3 weeks, and has a decreased trend at 9 weeks in diabetic rats compared with controls. CONCLUSIONS: Diabetes causes temporal alterations in the penis, and the significant changes in STZ rat model begin 3-9 weeks after induction. Further studies on the reversibility of the observed changes are warranted.
Assuntos
Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Disfunção Erétil/etiologia , Músculo Liso/fisiopatologia , Pênis/fisiopatologia , Animais , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Disfunção Erétil/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo I/metabolismo , Pênis/inervação , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE:: To evaluate the expression of endothelial and inducible NOS in addition to the miRNA-27b in the corpus cavernosum and peripheral blood of healthy rats, diabetic rats, alcoholic rats and rats with both pathologies. METHODS:: Forty eight Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D) and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study protein expressions of eNOS and iNOS by immunohistochemistry and expression of miRNA-27b in the corpus cavernosum and peripheral blood. RESULTS:: Immunohistochemistry for eNOS and iNOS showed an increase in cavernosal smooth muscle cells in the alcoholic, diabetic and alcoholic-diabetic groups when compared with the control group. Similarly, the mRNA levels for eNOS were increased in cavernosal smooth muscle (CSM) in the alcoholic, diabetic and alcoholic-diabetic groups and miRNA-27b were decreased in CSM in the alcoholic, diabetic and alcoholic-diabetic groups. CONCLUSION:: The major new finding of our study was an impairment of relaxation of cavernosal smooth muscle in alcoholic, diabetic, and alcoholic-diabetic rats that involved a decrease in the nitric oxide pathway by endothelium-dependent mechanisms accompanied by a change in the corpus cavernosum contractile sensitivity.
Assuntos
Alcoolismo/metabolismo , Diabetes Mellitus Experimental/metabolismo , MicroRNAs/análise , Óxido Nítrico Sintase Tipo III/análise , Óxido Nítrico Sintase Tipo II/análise , Pênis/química , Alcoolismo/complicações , Alcoolismo/fisiopatologia , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Imuno-Histoquímica , Masculino , Pênis/fisiopatologia , Ratos , Ratos WistarRESUMO
Abstract Purpose: To evaluate the expression of endothelial and inducible NOS in addition to the miRNA-27b in the corpus cavernosum and peripheral blood of healthy rats, diabetic rats, alcoholic rats and rats with both pathologies. Methods: Forty eight Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D) and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study protein expressions of eNOS and iNOS by immunohistochemistry and expression of miRNA-27b in the corpus cavernosum and peripheral blood. Results: Immunohistochemistry for eNOS and iNOS showed an increase in cavernosal smooth muscle cells in the alcoholic, diabetic and alcoholic-diabetic groups when compared with the control group. Similarly, the mRNA levels for eNOS were increased in cavernosal smooth muscle (CSM) in the alcoholic, diabetic and alcoholic-diabetic groups and miRNA-27b were decreased in CSM in the alcoholic, diabetic and alcoholic-diabetic groups. Conclusion: The major new finding of our study was an impairment of relaxation of cavernosal smooth muscle in alcoholic, diabetic, and alcoholic-diabetic rats that involved a decrease in the nitric oxide pathway by endothelium-dependent mechanisms accompanied by a change in the corpus cavernosum contractile sensitivity.
Assuntos
Animais , Masculino , Ratos , Pênis/química , MicroRNAs/análise , Diabetes Mellitus Experimental/metabolismo , Alcoolismo/metabolismo , Óxido Nítrico Sintase Tipo II/análise , Óxido Nítrico Sintase Tipo III/análise , Pênis/fisiopatologia , Imuno-Histoquímica , Ratos Wistar , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Alcoolismo/complicações , Alcoolismo/fisiopatologiaRESUMO
Androgen deficiency is strongly associated with erectile dysfunction (ED). Inadequate penile arterial blood flow is one of the major causes of ED. The blood flow to the corpus cavernosum is mainly derived from the internal pudendal arteries (IPAs); however, no study has evaluated the effects of androgen deprivation on IPA's function. We hypothesized that castration impairs IPAs reactivity and structure, contributing to ED. In our study, Wistar male rats, 8-week-old, were castrated and studied 30 days after orchiectomy. Functional and structural properties of rat IPAs were determined using wire and pressure myograph systems, respectively. Protein expression was determined by Western blot and immunohistochemistry. Plasma testosterone levels were determined using the IMMULITE 1000 Immunoassay System. Castrated rats exhibited impaired erectile function, represented by decreased intracavernosal pressure/mean arterial pressure ratio. IPAs from castrated rats exhibited decreased phenylephrine- and electrical field stimulation (EFS)-induced contraction and decreased acetylcholine- and EFS-induced vasodilatation. IPAs from castrated rats exhibited decreased internal diameter, external diameter, thickness of the arterial wall, and cross-sectional area. Castration decreased nNOS and α-actin expression and increased collagen expression, p38 (Thr180/Tyr182) phosphorylation, as well as caspase 3 cleavage. In conclusion, androgen deficiency is associated with impairment of IPA reactivity and structure and increased apoptosis signaling markers. Our findings suggest that androgen deficiency-induced vascular dysfunction is an event involving hypotrophic vascular remodeling of IPAs.