Spray-dried co-amorphous Tadalafil ternary mixtures: a promising platform towards the enhancement of solubility and bioavailability

Abstract Tadalafil (Tad) is a poorly water-soluble drug (BCS class II) that is used for the treatment of erectile dysfunction. An enhancement of aqueous solubility is vital to accelerate its onset of action and subsequently enhance its therapeutic effect. Binary and ternary mixtures of Tad with different amino acids (histidine, valine, alanine or arginine) and other excipients (mannitol and SLS) were prepared and then spray dried. The solubilizing efficiency and physicochemical characterization of all spray dried mixtures of Tad were studied. The optimum formulation was investigated in male rats to determine the onset of erection and the pharmacokinetic parameters of Tad. In general terms, the drug solubility of spray-dried formulae was enhanced compared to the crystalline form of the drug as a result of the formation of co-amorphous structures. The final result revealed that the Tad/alanine/mannitol spray-dried mixture (F10) showed the highest solubility and an improvement in its physicochemical characteristics. Moreover, F10 showed a significantly faster erection in rats with an improvement in Tad pharmacokinetic parameters when compared to the crystalline drug. Thus, F10 is selected as a promising formulation that successfully enhanced the bioavailability and the therapeutic efficacy of Tad.

Morphological and molecular analysis of apoptosis in the corpus cavernosum of rats submitted to a chronic alcoholism model.

PURPOSE: To evaluate the effect of chronic alcoholism on morphometry and apoptosis mechanism and correlate with miRNA-21 expression in the corpus cavernosum of rats. METHODS: Twenty-four rats were divided into two experimental groups: Control (C) and Alcoholic group (A). After two weeks of an adaptive phase, rats from group A received only ethanol solution (20%) during 7 weeks. The morphometric and caspase-3 immunohistochemistry analysis were performed in the corpus cavernosum. The miRNA-21 expression was analyzed in blood and cavernous tissue. RESULTS: Chronic ethanol consumption decreased cavernosal smooth muscle area of alcoholic rats. The protein expression of caspase 3 in the corpus cavernosum was higher in A compared to the C group. There was no difference in the expression of miRNA-21 in serum and cavernous tissue between the groups. CONCLUSION: Chronic ethanol consumption reduced smooth muscle area and increased caspase 3 in the corpus cavernosum of rats, without altered serum and cavernosal miR-21 gene expression.

Morphological and molecular analysis of apoptosis in the corpus cavernosum of rats submitted to a chronic alcoholism model

Abstract Purpose To evaluate the effect of chronic alcoholism on morphometry and apoptosis mechanism and correlate with miRNA-21 expression in the corpus cavernosum of rats. Methods Twenty-four rats were divided into two experimental groups: Control (C) and Alcoholic group (A). After two weeks of an adaptive phase, rats from group A received only ethanol solution (20%) during 7 weeks. The morphometric and caspase-3 immunohistochemistry analysis were performed in the corpus cavernosum. The miRNA-21 expression was analyzed in blood and cavernous tissue. Results Chronic ethanol consumption decreased cavernosal smooth muscle area of alcoholic rats. The protein expression of caspase 3 in the corpus cavernosum was higher in A compared to the C group. There was no difference in the expression of miRNA-21 in serum and cavernous tissue between the groups. Conclusion Chronic ethanol consumption reduced smooth muscle area and increased caspase 3 in the corpus cavernosum of rats, without altered serum and cavernosal miR-21 gene expression.

Functional and structural changes in internal pudendal arteries underlie erectile dysfunction induced by androgen deprivation.

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.

The relationship between histological prostatitis and lower urinary tract symptoms and sexual function.

This prospective analysis assessed the effect of histological prostatitis on lower urinary tract functions and sexual function. The patients were separated into two groups as histologically observed prostatitis (Group A) and no prostatitis (Group B) according to the biopsy outcomes. International prostate symptom score, international index of erectile function-5 scores, maximal and average flow rate, and residual urine volumes were compared statistically between groups. There was no significant difference (P>0.05) in baseline age (t=0.64), body mass index value (t=0.51), prostate volume (t=0.87), prostate-specific antigen levels (t=0.43), maximal (t=0.84) and average flow rate (t=0.59), and post-void residual urine volume (t=0.71). Mean international prostate symptom score in patients with prostatitis was numerically but not significantly higher than that in those without prostatitis (t=0.794, P=0.066). Mean international index of erectile function-5 score in the prostatitis group was significantly lower than that in those without prostatitis (t=1.854, P=0.013). Histological prostatitis notably affected sexual function of patients and may serve as a major risk factor for sexual dysfunction while having little effect on lower urinary tract symptoms.

The relationship between histological prostatitis and lower urinary tract symptoms and sexual function

ABSTRACT This prospective analysis assessed the effect of histological prostatitis on lower urinary tract functions and sexual function. The patients were separated into two groups as histologically observed prostatitis (Group A) and no prostatitis (Group B) according to the biopsy outcomes. International prostate symptom score, international index of erectile function-5 scores, maximal and average flow rate, and residual urine volumes were compared statistically between groups. There was no significant difference (P>0.05) in baseline age (t=0.64), body mass index value (t=0.51), prostate volume (t=0.87), prostate-specific antigen levels (t=0.43), maximal (t=0.84) and average flow rate (t=0.59), and post-void residual urine volume (t=0.71). Mean international prostate symptom score in patients with prostatitis was numerically but not significantly higher than that in those without prostatitis (t=0.794, P=0.066). Mean international index of erectile function-5 score in the prostatitis group was significantly lower than that in those without prostatitis (t=1.854, P=0.013). Histological prostatitis notably affected sexual function of patients and may serve as a major risk factor for sexual dysfunction while having little effect on lower urinary tract symptoms.

Fibrotic protein expression profiles in penile tissue of patients with erectile dysfunction.

OBJECTIVE: To characterize transforming growth factor beta 1 (TGFß1) and related signaling pathway proteins in a large cohort of human penile tissue (HPT) samples. METHODS: HPT was collected from patients undergoing penile prosthesis implantation for erectile dysfunction (ED) and divided into the following 2 groups: postradical prostatectomy ED (RP-ED; n = 57) and organic ED (O-ED; n = 30). HPT from patients undergoing partial penectomy without ED was used as controls (CON; n = 6). Western blot analysis was performed to investigate the protein expressions of TGFß1, thrombospondin 1 (TSP1; an activator of TGFß1), fibronectin (an extracellular matrix glycoprotein induced by TGFß1), and a family of transcriptional factors activated by TGFß1 (Smad2, phospho-Smad2-serine-465/467 [pSmad2], Smad3, phospho-Smad3-serine-423/425 [pSmad3]). RESULTS: Expressions of TGFß1 and TSP1 were significantly higher in RP-ED (P <.05) and O-ED (P <.05) groups compared with that of the CON group and were not different between either ED groups. Expressions of Smad2, pSmad2, Smad3, pSmad3, and fibronectin were similar among all groups. Within the RP-ED group, a subgroup analysis showed that time from RP to penile prosthesis implantation was related to increased expression of pSmad2 (P <.05), and previous history of intracavernosal injection was related to increased expression of TGFß1 (P <.05). CONCLUSION: Our results demonstrate that TSP1- and TGFß1-dependent fibrotic changes occur in penile tissue in patients with ED regardless of etiology. The unchanged expression of the Smad transcriptional factors may be reconciled by a Smad-independent downstream signaling pathway transmitting TGFß1 signals.

Endothelial nitric oxide synthase genotypes and haplotypes modify the responses to sildenafil in patients with erectile dysfunction.

Erectile dysfunction (ED) is usually treated with sildenafil. Although genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may impair endogenous NO formation, there is little information about how eNOS polymorphisms and haplotypes affect the responses to sildenafil. We studied 118 patients; 63 patients had ED secondary to radical prostatectomy (PED) and 55 had organic, clinical ED. eNOS genotypes for three eNOS polymorphisms (T(-786)C, rs2070744; a variable number of tandem repeats (VNTR) in intron 4; and Glu298Asp, rs1799983) were determined, and eNOS haplotypes were estimated using PHASE 2.1. The clinical responses to sildenafil were evaluated and the patients were classified as good responders (GR) or poor responders (PR) when their changes in five-item version of International Index for Erectile Function questionnaire were above or below the median value. The TC/CC genotypes and the C allele for the T(-786)C polymorphism were more common in GR, compared with PR patients with PED. However, the 4b4a/4a4a genotypes and the 4a allele for the VNTR polymorphism in intron 4 were more common in GR, compared with PR patients with clinical ED. The C-4a-Glu haplotype was more common in GR than in PR patients with PED. Conversely, the T-4b-Asp haplotype was less common in GR than in PR patients with PED. No other significant differences were found. Our findings show evidence that eNOS polymorphisms affect the responses of PED and clinical ED patients to sildenafil.

Papel da disfunção erétil como manifestação sentinela e marcador de risco para doença coronariana / Role of erectile dysfunction as a sentinel event and risk marker for coronary disease

INTRODUÇÃO: A doença cardiovascular é a causa mais comum de morte em todo o mundo. Em homens, 50% das mortes por doença arterial coronariana ocorre em indivíduos sem história prévia de doença cardiovascular. Disfunção erétil e doença arterial coronariana têm uma relação estreita, já que ambas são consequências de disfunção endotelial, levando a limitações no fluxo sanguíneo. A associação entre severidade da disfunção erétil e a extensão das lesões da doença arterial coronariana ao exame angiográfico sugere que homens com disfunção erétil sejam considerados sob risco aumentado de doença arterial coronariana. OBJETIVO: Avaliar o papel da disfunção erétil como manifestação sentinela e/ou marcador de risco para doença arterial coronariana. MÉTODOS: Realizou-se uma análise secundária com dados previamente coletados em dois projetos (“Projeto Avaliar” e “Projeto Ampliar”). Pacientes do sexo masculino, com idade >18 anos, foram convidados a participar das duas pesquisas sobre disfunção erétil ao comparecerem a uma consulta médica ambulatorial em 2002-2003 (Projeto Avaliar) e em 2003-2004 (Projeto Ampliar)...

INTRODUCTION: Cardiovascular disease is the most common cause of death worldwide. In men, 50% of deaths due to coronary artery disease occur among those without previous history of cardiovascular disease. Erectile dysfunction and coronary artery disease are closely related, since they are both consequences of endothelial dysfunction, leading to restrictions on the blood flow. The association between the severity of erectile dysfunction and the angiographic extension of coronary artery disease suggests that men with erectile dysfunction be considered at increased risk for coronary artery disease. OBJECTIVES: To evaluate the role of erectile dysfunction as a sentinel sign and/or surrogate of risk for coronary artery disease. METHODS: We performed a secondary analysis on data previously collected in two research projects (“Projeto Avaliar” e “Projeto Ampliar”). Male patients, age 18 years old or more, were invited to participate in two surveys about erectile dysfunction while attending a routine office visit or consultation in 2002-2003 (Projeto Avaliar) and in 2003-2004 (Projeto Ampliar)...

Risk factors of Peyronie's disease. What does our clinical experience show?

INTRODUCTION: Peyronie's disease (PD) is a localized fibrosis that affects the tunica albuginea of the penis. Its origin can be associated with coital penile trauma in men with autoimmune hypersensitivity and a presumed genetic predisposition. AIM: To identify clinical and traumatic risk factors in a patient population with PD, when compared to a control group. METHODS: From November 2007 to March 2010, 317 patients sought medical attention for PD. As control group, 147 consecutive patients, who came for a prostate exam, were studied. Clinical, traumatic, and sexual history of these patients was gathered. Risks factors were considered only if they had been present before the onset of PD symptoms. MAIN OUTCOME MEASURE: The International Index of Erectile Function and the International Prostate Symptoms Score. A univariate logistic regression model (chi-square) (odds ratios [ORs] and 95% confidence intervals [CI]) was used to estimate the association of risk factors with PD; and the Student's t-test was implemented for age. RESULTS: The mean age of patients with PD and control group was 56.7 and 58.8, respectively (P<0.923). The mean evolution time of the disease was 17.7 months (2-48). Erectile dysfunction (ED) and coital trauma constituted the only two independent risk factors for PD compared to the control group (P<0.05 and 0.002, respectively) with an OR of 1.5 (95% CI 1.0-2.3) and 2.69 (95% CI 1.41-5.21), respectively. Patients with ED and diabetes mellitus and with a mild-to-moderate ED also presented a higher predisposition (P=0.008 and 0.00001), with an OR of 3.64 (95% CI 1.33-10.79) and 5.58 (95% CI 3.03-10.42), respectively. CONCLUSION: Erectile dysfunction and coital trauma have proven to be independent risk factors for the development of PD.

Age-related morphological changes in smooth muscle and collagen content in human corpus cavernosum.

INTRODUCTION: Aging process has been related to erectile dysfunction (ED) possibly due to morphological changes in corpus cavernosum among many other causes. AIM: To evaluate smooth muscle and collagen content in human corpus cavernosum and to correlate it to age. METHODS: Cadaveric human cavernosal tissue was collected during the period of 1 year. Morphological analysis of a whole corpus cavernosum was performed in tissue sections stained with Masson's trichromic method to differentiate smooth muscle (red) from collagen (blue) content. MAIN OUTCOME MEASURES: Analysis was performed with specialized micrographs image analysis software. Pearson's correlation test was used to establish correlation between corpus cavernosum morphology (smooth muscle and collagen content) and age. RESULTS: A total sample of 89 tissues from different male cadavers were analyzed. The average age of the sample was 49.2 ± 19.1 years, with a range between 14 and 90 years. There was a statistically significant inverse correlation between age and the percentage of smooth muscle content (P = 0.012), direct correlation between age and percentage of collagen content (P = 0.019), and inverse correlation between age and the ratio of smooth muscle : collagen content (P = 0.007). CONCLUSIONS: Age-related morphological changes in terms of smooth muscle and collagen content are observed in human corpus cavernosum as a possible contributing factor to the development of ED.

Disfunção erétil: um marcador precoce de doenças cardiovasculares / Erectile dysfunction: an early marker of cardiovascular diseases

A disfunção erétil tem fatores de risco similares aos das doenças cardiovasculares, mas também pode ser um fator de risco independente para tais doenças. As evidências atuais consideram a disfunção erétil como uma desordem primordialmente de origem vascular e, mais do que isso, como um marcador precoce das doenças cardiovasculares. Apesar disso, o potencial da disfunção erétil como um sinal para alertar os médicos para uma possível manifestação precoce de doenças cardiovasculares mais graves tem sido pouco explorado na prática clínica diária.

Avaliação da qualidade de vida e disfunções sexuais em pacientes com insuficiência renal crônica em tratamento dialítico em hospital / Evaluation of quality of life and sexual dysfunctions in chronic renal failure patients undergoing hemodialysis in a hospital

Disfunção erétil é definida como a incapacidade persistente de obter e/ou manter uma ereção suficiente paraum desempenho sexual satisfatório, com prevalência de 52% em homens com idade de 40 a 70 anos, segundoo Massachusetts Male Aging Study. É uma condição bastante prevalente em pacientes portadores deinsuficiência renal crônica em tratamento dialítico, tendo como etiologia múltiplos fatores orgânicos epsicológicos, e que se manifesta fundamentalmente no homem por diminuição da libido e disfunção erétil. Oobjetivo desse estudo foi avaliar a qualidade de vida de pacientes do sexo masculino, com disfunção erétil,portadores de insuficiência renal crônica em hemodiálise no Hospital de Base de São José do Rio Preto –FAMERP. Foram analisados prontuários de 13 pacientes, coletando-se valores laboratoriais de testosteronasérica livre, creatinina sérica e respostas de questionário sobre qualidade de vida e o Índice Internacional deFunção Erétil (IIFE). A média de idade foi de 45,69 ± 12,12 anos, o valor médio da testosterona sérica foi de9,51 pg/ml ± 3,17, e o valor médio de creatinina sérica foi de 12,43 mg/dL ± 2,97. A Disfunção Erétil foi severaem 23%, moderada em 23% e leve em 54%. Todos os pacientes avaliados apresentavam desejo sexualpreservado, embora não com a mesma intensidade. Em relação ao questionário sobre qualidade de vida, 47%sentiriam-se muito insatisfeitos, 38% um pouco insatisfeitos e 15% nem satisfeitos nem insatisfeitos casopermanecessem com a função erétil que possuíam para o resto da vida. A Disfunção Erétil ocorre independentedos níveis séricos de testosterona livre, o que é justificado pela permanência do desejo sexual. É justificada,portanto, pela interação dos distúrbios orgânicos, emocionais e da condição a que o doente é submetido,com conseqüente agravo na qualidade de vida.

Erectile Dysfunction is defined as the incapacity to obtain and/or maintain an effective erection for asatisfactory sexual performance, affecting 52% of men aged 40 to 70 years, according to the MassachusettsMale Aging Study. It is a prevalent condition in patients with chronic renal failure undergoing hemodialysis.It has as etiology multiple organic and psychological factors, which finds expression mainly in the erectiledysfunction and reduction of men’s libido . The objective of this study was to evaluate the quality of life ofmale patients with erectile dysfunction, carriers of chronic renal failure in hemodialisys in Hospital de Base deSão José do Rio Preto - FAMERP. Medical charts of 13 patients have been analyzed, collecting laboratorialvalues of free serum testosterone, serum creatinine and answers of a questionnaire on quality of life and theInternational Index of Erectile Function (IIEF). The average age was 45.69 ± 12.12 years, the average value ofthe serum testosterone was 9.51 pg/ml ± 3.17, and the average value of serum creatinine was 12.43 mg/dL ±2.97. The Erectile Dysfunction was severe in 23%, moderate in 23% and mild in 54%. All the evaluatedpatients presented preserved sexual desire, even though with no same intensity. In relation to thequestionnaire on quality of life, 47% felt very unsatisfied, 38% a little unsatisfied and 15% neither satisfiednor unsatisfied in case that they could remain with the present erectile function for the rest of their life. TheErectile Dysfunction occurs independently from the serum levels of free testosterone; that is, by thepermanence of the sexual desire. It is justified, therefore, by the interaction of the organic and emotionaldisorders, and by the condition that the patient is submitted, worsening their quality of life.

Evaluación de la respuesta al sildenafil 50 mg en pacientes con disfunción eréctil sin tratamientos previos en la práctica cotidiana / Evaluation of the response to sildenafil 50 mg in patients with erectil dysfunction without previous treatment during the current practice

Nuestro estudio corrobora la elevada eficacia del Sildenafil para el tratamiento de la Disfunción Sexual Eréctil en el contexto de la práctica diaria de consultorio. El Sildenafil mostró ser un fármaco seguro, aun en pacientes con patologías concomitantes, debiendo pocos pacientes suspender la medicación por efectos secundarios severos. El Sildenafil mejoró no sólo la actividad sexual de los pacientes sino también su calidad de vida.

Comparative analysis of the penis corpora cavernosa in controls and patients with erectile dysfunction.

OBJECTIVE: To evaluate the presence of structural disorders of the corpora cavernosa in patients with erectile dysfunction (ED), as despite new drugs being effective in many men with ED, some aspects of structural disorders of the corpora cavernosa remain unknown. MATERIALS AND METHODS: Biopsy specimens were taken from the corpora cavernosa of seven patients (mean age 57.8 years, range 51-72) with severe ED who had a penile prosthesis implanted. The controls tissues were fragments of corpora cavernosa obtained from autopsies of six men (mean age 52.3 years, range 40-66) who died from causes unrelated to the urogenital system. For light microscopy, the specimens were processed routinely to paraffin wax, and by immunohistochemistry to evaluate elastic fibres, and by Masson's trichrome to analyse collagen and smooth muscle fibres. Stereological methods were used to quantitatively evaluate the different elements (as a percentage). RESULTS: The percentages of the different elements in the human penis of controls and men with ED, respectively, were: elastic fibres 13.2% and 9.1%; collagen fibres 40.8% and 41.6%; and smooth muscle, 40.4% and 42%. CONCLUSIONS: In patients with ED there was a statistically significant reduction in the percentage of elastic fibres, but no statistically significant difference in collagen and smooth muscle fibres, and no appreciable differences in collagen distribution between the groups.

Histomorphometry of penile smooth muscle fiber in severe erectile dysfunction

CONTEXTO E OBJETIVO: A fibra muscular lisa apresenta fundamental importância no mecanismo de ereção e alterações em sua função ou em sua quantidade podem estar associadas à disfunção erétil. O objetivo do estudo é analisar a proporção de fibras musculares lisas em pacientes com disfunção erétil grave. TIPO DE ESTUDO E LOCAL: Estudo clínico, realizado no Grupo de Disfunção Erétil da Universidade Federal de São Paulo (Unifesp) e no Laboratório de Anatomia e Urologia da Universidade Estadual do Rio de Janeiro (UERJ). MÉTODOS: 20 pacientes com disfunção erétil grave de acordo com o Indice Internacional de Função Erétil e Teste de Ereção Fármaco-Induzida divididos em dois grupos de 10 pacientes, sendo um com fluxo arterial normal (44 a 78 anos, média @ 63 anos) e o outro com fluxo arterial alterado (38 a 67 anos, média @ 56,2 anos) ao duplex ultra-som. Os resultados são comparados com um grupo formado por 10 cadáveres de 18 a 25 anos (média @ 21,6 anos) presumidamente potentes. A quantificação das fibras musculares lisas foi realizada a partir de estudo imunoistoquímico com anticorpo anti-actina e análise computadorizada da imagem pelo sistema HSL (matiz, saturação e luminosidade). RESULTADOS: A proporção de fibras musculares lisas encontradas foi de 41,15 por cento para o grupo controle. Os pacientes com disfunção erétil apresentaram 27,24 por cento de fibras musculares lisas para o grupo com fluxo arterial normal e 25,74 por cento para o grupo com fluxo arterial insuficiente. Com exceção de apenas um paciente (do grupo com fluxo arterial normal), 19 pacientes apresentavam ao menos uma doença crônica ou fator de risco para disfunção erétil, destacando-se diabetes mellitus, hipertensão arterial sistêmica e tabagismo, nesta ordem. CONCLUSAO: Nos pacientes com disfunção erétil grave, o fluxo arterial isoladamente não apresenta interferência na proporção de fibras musculares lisas, pois os resultados foram semelhantes. Nestes pacientes com disfunção grave, a diminuição das fibras musculares lisas em relação ao grupo controle pode decorrer das doenças crônicas e de seu potencial aterosclerótico.

Histomorphometry of penile smooth muscle fiber in severe erectile dysfunction.

CONTEXT AND OBJECTIVE: Smooth muscle fiber has fundamental importance in erection. Alterations in its function or quantity may be associated with erectile dysfunction. The study objective was to assess the proportion of penile smooth muscle fiber in patients with severe erectile dysfunction. DESIGN AND SETTING: Clinical study, in the Sexual Dysfunction Group, Universidade Federal de São Paulo (Unifesp), and in the Anatomy Laboratory, Universidade Estadual do Rio de Janeiro (UERJ). METHODS: Twenty patients with severe erectile dysfunction were selected to form two groups of ten patients: one with normal arterial flow (age range: 44 to 78 years) and the other with altered arterial flow (age range: 38 to 67 years). These groups were compared with a group formed by ten cadavers aged 18 to 25 years that were presumed to have been potent. Quantification of the smooth muscle fibers was done by means of an immunohistochemical study. RESULTS: The proportion of smooth muscle fiber found was 41.15% for the control group. The patients with erectile dysfunction and normal arterial flow presented 27.24% and those with altered arterial flow presented 25.74%; 19 patients presented at least one chronic disease or risk factor for erectile dysfunction, with prominence for diabetes mellitus, systemic arterial hypertension and smoking. CONCLUSION: Among patients with severe erectile dysfunction, the arterial flow on its own does not present interference in the proportion of smooth muscle fiber. The diminution of the proportion of smooth muscle fiber may result from chronic diseases and vascular risk factors.

Different effect of losartan and amlodipine on penile structures in male spontaneously hypertensive rats.

BACKGROUND: Erectile dysfunction is highly prevalent in hypertensive patients. Since both angiotensin II receptor type-1 blockers (ARBs) and calcium antagonists are current and effective antihypertensive drugs, the aim of this study was to determine possible differences between ARBs and calcium antagonists concerning the protection of penile structures from the deleterious effects of arterial hypertension. METHODS AND RESULTS: During 6 months, 3 groups of male spontaneously hypertensive rats (SHR) and 1 of Wistar-Kyoto (WKY) rats, as a control group, were studied: SHR without treatment; SHR with losartan (L) 30 mg/kg/day; SHR with amlodipine (A) 3 mg/kg/day, and WKY without treatment. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries, cavernous tissue fibrosis and collagen type III (COL III) were evaluated. After 6 months, SHR+L and SHR+A showed a similar reduction in blood pressure compared with untreated SHR. However, only SHR+L and control WKY presented significantly lower values of: CSM (p < 0.01), VSM (p < 0.01), and COL III (p < 0.01) when compared with either untreated SHR or SHR+A. There was also a positive correlation between left ventricular mass and proteinuria with VSM from cavernous arteries, CSM and COL III in untreated SHR and SHR+A. These relations were not present in SHR+L and WKY. CONCLUSION: Although losartan and amlodipine achieved similar blood pressure control, losartan but not amlodipine showed a significant protective role against structural changes in the vessels and cavernous spaces of the erectile tissue caused by arterial hypertension.