RESUMEN
AIM: We studied whether available oxygen without induced mechanical stretch regulates the release of the biologically active B-type natriuretic peptide (BNP) from Langendorff heart. METHODS: Rat hearts were isolated and perfused with a physiological Krebs-Henseleit solution at a constant hydrostatic pressure in Langendorff set-up. The basal O2 level of perfusate (24.4 ± 0.04 mg L-1 ) was gradually lowered to 3.0 ± 0.01 mg L-1 over 20 min using N2 gas (n = 7). BNP and O2 level were measured from coronary flow. During control perfusions (n = 5), the O2 concentration was kept at 26.6 ± 0.3 mg L-1 . RESULTS: A low oxygen concentration in the perfusate was associated with a significant increase in BNP release (F = 40.4, P < 0.001). Heart rate decreased when the oxygen concentration in the perfusate reached 9.1 ± 0.02 mg L-1 and continued to fall in lower oxygen concentrations (F = 14.8, P < 0.001). There was also a significant but inverse correlation between BNP and oxygen in the coronary flow (R2 = 0.27, P < 0.001). CONCLUSION: In the spontaneously beating Langendorff rat heart, a decreasing concentration of oxygen in the ingoing perfusion increased the secretion of BNP. The effect of oxygen was independent of mechanical stretch of the heart as it occurred even when the heart rate decreased but the pressure conditions remained constant. The difference in the oxygen capacitance of blood and Krebs-Henseleit solution appears to be a major factor affecting secretion of BNP, which is correlated with the oxygen tension of myocardial cells and affected both by the oxygen concentration and capacitance of solution perfusing the heart and by the coronary flow.
Asunto(s)
Hipoxia/metabolismo , Miocardio/metabolismo , Péptido Natriurético Encefálico/metabolismo , Animales , Corazón/metabolismo , Preparación de Corazón Aislado , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To test the hypothesis that men with a history of undescended testicle have voiding problems similar to those in rodents exposed to excessive amounts of oestrogens during development, although the role of oestrogen in the failure of the human testicle to descend remains controversial. PATIENTS AND METHODS: Thirteen men (mean age 45 years) previously operated on for an undescended testicle (testis-retention, TR group) and 12 age-matched men operated on for inguinal hernia or appendicitis (control group) participated in a urodynamic examination, transrectal ultrasonography (TRUS) of the prostate, and blood tests for hormones and prostate-specific protein. They also completed a questionnaire on urinary symptoms. RESULTS: The free maximum flow rate was significantly lower and the detrusor pressure at maximum flow (P(det)Q(max)) slightly higher in the TR than the control group. Three men in the TR group (and none of the controls) had bladder outlet obstruction (BOO), whereas voiding was not obstructed among 11 control men (and five men in the TR group). The hormone concentrations of the groups did not differ significantly but the prostates were significantly smaller in the TR group. The testosterone concentrations and the ratio between 17beta-oestradiol (E2) and free testosterone (E2/fT) influenced prostate size significantly. An exploratory analysis suggested that E2/fT may influence the maximum detrusor pressure and P(det)Q(max). CONCLUSION: Men born with an undescended testicle had smaller prostates but more often had BOO than did the controls. The results suggest that an imbalance between the actions of oestrogen and testosterone may influence the initiation and continuance of BOO among cryptorchid men.
Asunto(s)
Criptorquidismo/cirugía , Obstrucción del Cuello de la Vejiga Urinaria/etiología , Retención Urinaria/etiología , Adulto , Criptorquidismo/fisiopatología , Estrógenos/sangre , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Enfermedades de la Próstata/diagnóstico por imagen , Enfermedades de la Próstata/fisiopatología , Testosterona/sangre , Ultrasonografía , Obstrucción del Cuello de la Vejiga Urinaria/fisiopatología , Retención Urinaria/fisiopatología , UrodinámicaRESUMEN
Expression of cyclooxygenase-2 (E. C. 1.14.99.1) in prostate and the lower urinary tract (LUT) of the neonatally estrogenized male rat has been studied by using a COX-2's PCR fragment of 724 nt spanning 3 introns and a 478nt internal standard for quantitative RT-PCR. The same fragment of 724 nt was used for RNA probe in Northern hybridization. Neonatal estrogenization (10 microg/day of diethylstilbestrol on days 1-5) had no effect on COX-2 expression in prostatic urethra, prostatic lobes, or bladder. Acute estrogen treatment of castrated animals did not induce COX-2 expression, either. In addition the differential expression of basal level of COX-2 in the different lobes of prostate in normal rat was demonstrated. Our results suggest a constant expression of COX-2 gene in prostate and the lower urinary tract of the neonatally estrogenized (neoDES) rats. The present study indicates that the increased expression of COX-2 is probably not essential for the estrogen-driven development of stromal inflammation or hyperplastic and dysplastic alterations in the prostate of neoDES rats.
Asunto(s)
Dietilestilbestrol/farmacología , Regulación Enzimológica de la Expresión Génica/fisiología , Isoenzimas/genética , Prostaglandina-Endoperóxido Sintasas/genética , Próstata/enzimología , Uretra/enzimología , Vejiga Urinaria/enzimología , Animales , Animales Recién Nacidos , Ciclooxigenasa 2 , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Masculino , Orquiectomía , Próstata/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Uretra/efectos de los fármacos , Vejiga Urinaria/efectos de los fármacos , Conducto Deferente/efectos de los fármacos , Conducto Deferente/enzimologíaRESUMEN
Aromatization of androgens is a key step in estrogen production, and it regulates the delicate balance between estrogens and androgens in the gonads and sex steroid target tissues. In the present study, we generated transgenic mice (AROM(+)) bearing the human ubiquitin C promoter/human P450 aromatase fusion gene. AROM(+) male mice are characterized by an imbalance in sex hormone metabolism, resulting in elevated serum E(2) concentrations, combined with significantly reduced testosterone and FSH levels, and elevated levels of PRL and corticosterone. AROM(+) males present a multitude of severe structural and functional alterations in the reproductive organs, such as cryptorchidism associated with Leydig cell hyperplasia, dysmorphic seminiferous tubules, and disrupted spermatogenesis. The males also have small or rudimentary accessory sex glands with abnormal morphology; a prominent prostatic utricle with squamous epithelial metaplasia, and edema in the ejaculatory ducts and vas deferens. In addition, the abdominal muscle wall is thin, and the adrenal glands are enlarged, with cortical hyperplasia. Some of the abnormalities, such as undescended testes and undeveloped prostate, resemble those observed in animals exposed perinatally to high levels of exogenous estrogen, indicating that the elevated aromatase activity results in excessive estrogen exposure during early phases of development. Some of the disorders in the reproductive organs, furthermore, can be explained by the fact that AROM(+) males are hypoandrogenic, and have elevated levels of serum PRL and corticosterone. Thus, the AROM(+) mouse model provides a novel tool to investigate the consequences of a prolonged increase in conversion of androgens to estrogens which results in complex hormonal disturbances altering the structure and function of various male reproductive organs.
Asunto(s)
Aromatasa/genética , Expresión Génica , Músculos Abdominales/anomalías , Corteza Suprarrenal/patología , Animales , Corticosterona/sangre , Criptorquidismo/enzimología , Criptorquidismo/genética , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Genitales Masculinos/anomalías , Humanos , Hiperplasia , Células Intersticiales del Testículo/patología , Masculino , Ratones , Ratones Transgénicos , Prolactina/sangre , Regiones Promotoras Genéticas , Próstata/anomalías , Proteínas Recombinantes de Fusión , Túbulos Seminíferos/anomalías , Espermatogénesis/genética , Testosterona/sangre , Ubiquitinas/genéticaRESUMEN
PURPOSE: Bladder outlet obstruction develops in estrogen treated males. Because of the lack of electromyography recordings, earlier studies have not clarified the failure mechanisms of voiding. We simultaneously recorded electromyography activity of the proximal rhabdosphincter in neonatally estrogenized rats with transvesical cystometry and urethral flow, followed by morphometric analysis of the urethral structure. MATERIALS AND METHODS: Rats treated neonatally with 10 microg. diethylstilbestrol daily on days 1 to 5 after birth were used in urodynamics and morphological studies at ages 5 to 6.5 months. Using anesthesia the bladder, anterior surface of the proximal rhabdosphincter and distal urethra were exposed to record simultaneously the high frequency oscillations of intraluminal bladder pressure, and the rates of intermittent flow from the distal urethra and electromyography activity of the proximal rhabdosphincter with a suction electrode. RESULTS: Neonatally estrogenized rats had higher mean maximal bladder pressure plus or minus standard deviation (42.1 +/- 6.4 versus 37.7 +/- 4.9 mm. Hg, p = 0.01), decreased mean flow (2.3 +/- 0.1 versus 4.1 +/- 1.6 ml. per minute, p < 0.0001) and mean increment of proximal rhabdosphincter electromyography depolarization amplitude (3.0 +/- 0.78 versus 2.6 +/- 0.87 mV., p = 0.02) compared with controls, while mean transient repolarization was absent or highly decreased (-0.3 +/- 0.61 versus 0.3 +/- 0.9 mV., p = 0.04). Morphologically the proximal rhabdosphincter was atrophied with increased connective tissue. CONCLUSIONS: Alterations in the structure and electromyography activity of the urethral musculature imply that neonatal exposure to diethylstilbestrol predisposes male rats to urethral atrophy and dyssynergia, evident as altered electromyography activity of the proximal rhabdosphincter.
Asunto(s)
Dietilestilbestrol/farmacología , Estrógenos no Esteroides/farmacología , Contracción Muscular/efectos de los fármacos , Uretra/fisiopatología , Animales , Animales Recién Nacidos , Atrofia , Electromiografía , Femenino , Masculino , Músculo Liso/fisiopatología , Ratas , Ratas Endogámicas , Uretra/patología , Obstrucción del Cuello de la Vejiga Urinaria , UrodinámicaRESUMEN
Micturition requires high bladder pressure and simultaneous opening of the urethra. In adult male rat, a rhabdosphincter (RB) is known to be electrically active when the bladder pressure is high. This indicates a closure rather than an opening of the urethra, which is inconsistent with the requirements of optimal urodynamics. In order to solve this problem, we simultaneously recorded electromyogram (EMG) of the proximal RB, bladder pressure, and flow rate. Micturition was evoked by an increased volume of saline in the bladder. A computer-based recording device was used with minimal filtering. The EMG was recorded with a monopolar flexible suction electrode. The suction electrode records action potentials resembling those obtained with a microelectrode technique. During the early high-frequency intraluminal pressure oscillation period (IPHFO), the increase of pressure initially associated with a decrease of potential of the RB. When the first flow peak appeared, the relationship of the bladder pressure and RB single EMG activities changed. The increasing pressure coincided with the positive potential wave (depolarisation). It was interrupted by a transient negative polarity period called transient repolarisation (TRP) coinciding with a flow rate peak, thus indicating an opening of the RB lumen. After the TRP, the depolarisation continued. Additional experiments employing different methods are needed for positive identification of the TRP mechanism.
Asunto(s)
Músculo Liso/fisiología , Uretra/fisiología , Micción/fisiología , Animales , Electromiografía , Masculino , RatasRESUMEN
PURPOSE: Our previous studies indicate that neonatal estrogenization with diethylstilbestrol (neoDES) of male mice and rats causes partial outlet obstruction. In the present study, type XII and XIV collagens were localized in the bladder to study their role in the development of obstruction. MATERIALS AND METHODS: The bladder sections immunostained with smooth muscle specific a-actin antibody were double labeled either with collagen type XII or type XIV antibodies. The specimens were then analyzed with conventional and confocal fluorescence microscope. RESULTS: Type XII and XIV collagens were not evenly distributed in the bladder. Further, in neonatally estrogenized rats collagen XIV appeared inside smooth muscle fascicles. CONCLUSIONS: Non-overlapping distributions of collagen XII and XIV suggest their different roles in the urinary bladder. Penetration of collagen XIV inside smooth muscle fascicles may have a role in the development of DES-induced partial outlet obstruction.
Asunto(s)
Colágeno , Obstrucción del Cuello de la Vejiga Urinaria/patología , Vejiga Urinaria/patología , Animales , Colágeno/análisis , Masculino , Ratas , Vejiga Urinaria/químicaRESUMEN
Epidemiological studies suggest that diets rich in phytoestrogens (plant estrogens), particularly soy and unrefined grain products, may be associated with low risk of breast and prostate cancer. It has also been proposed that dietary phytoestrogens could play a role in the prevention of other estrogen-related conditions, namely cardiovascular disease, menopausal symptoms and post-menopausal osteoporosis. However, there is no direct evidence for the beneficial effects of phytoestrogens in humans. All information is based on consumption of phytoestrogen-rich diets, and the causal relationship and the mechanisms of phytoestrogen action in humans still remain to be demonstrated. In addition, the possible adverse effects of phytoestrogens have not been evaluated. It is plausible that phytoestrogens, as any exogenous hormonally active agent, might also cause adverse effects in the endocrine system, i.e. act as endocrine disrupters.