No abstract

Endothelins (ET) are a family of vasoactive peptides that act via two subtypes of receptors, named ETA and ETB. ET-1 binds to both ETA and ETB, whereas the isopeptide ET-3 preferentially binds to ETB. The localization of ETA and ETB receptors in the rat adrenal gland and their involvement in the adrenal secretagogue effect of ETs has been studied in vitro. Autoradiographic assessment of the selective displacement of [125I]ET-1, [125I]ET-3 and [125I]BQ-3020 (an ETB agonist) by BQ-123 or BQ-788 (specific antagonists of ETA and ETB, respectively) indicates that the zona glomerulosa and adrenal medulla possess both ETA and ETB, whereas the zona fasciculata/reticularis is exclusively provided with ETB. ET-1, ET-3 and BQ-3020 enhance aldosterone and corticosterone secretion by dispersed cells of the zona glomerulosa and zona fasciculata/reticularis, respectively. BQ-123 does not affect the secretagogue action of these three agonists, whereas BQ-788 completely annuls it. ET-1 induces a marked rise in catecholamine release by fragments of the adrenal medulla, and both BQ-123 and BQ-788 partially reverse this effect. ET-3 and BQ-3020 elicit a catecholamine release that is less intense than that produced by ET-1; this response is unaffected by BQ-123 and abolished by BQ-788. Thus, in the rat, the corticosteroid secretagogue effect of ETs seems to be exclusively mediated by the ETB receptor subtype, and the catecholamine secretagogue action by both ETA and ETB. The functional relevance of ETA receptors present in the zona glomerulosa remains to be investigated.

Considering that the muscles of the anus perform a critical role in maintaining continence, losses in their structure can negatively affect the physiological control of the intestinal contents. Anorectal electro-stimulation (ARES) has been reported to have a positive effect on the functionality of treated patients, but how ARES affects the structural tissues of the anorectal segment remains unknown. Because the study of how ARES structurally affects human tissues is not possible, this study aimed to clarify these effects in a murine model, which has a similar anorectal segment (structure and physiology) to humans. For the descriptive and comparative study, randomly selected nulliparous adult Wistar rats (n = 5) were submitted to 30 anorectal sessions of ARES with a biphasic current (700 μs, 50 Hz from 2 to 4 mA). After treatment, the animals were euthanized, and the anorectal segments were dissected and processed for histopathological analysis. Our results showed that ARES increased the widths of the mucosal, submucosal and muscle layers of the rectum, as well as the number of leukocytes in the mucosa. ARES also caused hyperplasia of the smooth muscle of the internal anal sphincter and hypertrophy of the external anal sphincter muscle. In conclusion, our results showed that ARES had not only a positive effect on the structure (morphology) of all tissues associated with the rectum and anus but, more importantly, on the structural gain of the muscles (hyperplasia and hypertrophy), which could point to a functional gain of the anal sphincter, reinforcing the applicability of ARES as a non-invasive treatment for anal incontinence.

Background: Cardiopathies are high prevalence conditions. Among them, rheumatic carditis is of high relevance in developing countries. Left cardiac chamber changes are associated to endothelial dysfunction and ET-1 levels increase. Pulmonary circulation is then affected, and not seldom leading to pulmonary hypertension (PH). However, the presence of ET-1 and its receptors in the mitral valve itself -promoting pulmonary vascular changes, with increased rheumatic valvular deformation -has not been discussed in the literature.

Objectives: Rheumatic fever is a highly prevalent disease in Brazil, and it poses a major public health problem. It is the leading cause of acquired heart disease in childhood and adolescence. The aim of this study was to evaluate the gene expression of ET-3 and its receptors, in replaced rheumatic mitral valves.Methods: We studied the gene expression of endothelin-3 (ET-3) and its receptors, endothelin receptor A and endothelin receptor B (ETr-A and ETr-B), in the rheumatic mitral valves of 17 patients who underwent valve replacement surgery. The samples also underwent a histological analysis.Results: Our data showed that almost all patients, regardless of individual characteristics such as gender or age, expressed the endothelin receptor genes, but did not express the genes for ET-3. In quantitative analysis, the ETr-A/GAPDH mean ratio was 33.04 ± 18.09%; while the ETr-B/GAPDH mean ratio was 114.58 ± 42.30%. Regarding histopathological individual features, the frequency of fibrosis is 100%, 88.23% of mononuclear infiltrate, 52.94% of neovascularization, 58.82% of calcification and absence of ossification.Conclusion: The presence of receptors ETr-A and ETr-B in rheumatic mitral valves suggests its interaction with the system of circulating endothelins, particularly ETr-B (known for acting in the removal of excess endothelin) detected in a greater proportion, which could explain the lack of expression of endothelin in rheumatic mitral valve, process to be elucidated.Descriptors: Rheumatic fever. Mitral valve stenosis. Endothelins.