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Doctoral Thesis
DOI
10.11606/T.42.2011.tde-16082011-090246
Document
Author
Full name
Fernando Silva Carneiro
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Passaglia, Rita de Cassia Aleixo Tostes (President)
Abdo, Carmita Helena Najjar
Bendhack, Lusiane Maria
Nucci, Gilberto de
Rossoni, Luciana Venturini
Title in Portuguese
Papel do fator de necrose tumoral (TNF-a) na fisiopatologia da disfunção erétil.
Keywords in Portuguese
Citocinas
Doenças cardiovasculares
Necrose
Óxido nítrico
Pênis
Abstract in Portuguese
A disfunção erétil (DE) tem sido associada com doenças cardiovasculares (CVD), as quais se caracterizam por níveis elevados de citocinas pró-inflamatórias, tais como o fator de necrose tumoral a (TNF-a). Este estudo testa a hipótese de que o TNF-a altera a reatividade do corpo cavernoso (CC), favorecendo a disfunção erétil. O CC de animais infundidos com TNF-a apresentou: 1) diminuição do relaxamento mediado por nervos não-adrenérgicos não-colinérgicos (NANC); 2) aumento das contrações mediadas por nervos simpáticos; 3) diminuição da expressão gênica da sintase de óxido nítrico endotelial (eNOS) e neuronal (nNOS). O CC de animais nocaute do TNF-a apresentou aumento no relaxamento dependente do endotélio, no relaxamento mediado por nervos NANC e na expressão da eNOS e nNOS. As contrações mediadas por nervos simpáticos estão diminuídas no CC destes animais. Em conjunto, o presente trabalho demonstra que o TNF-a exerce um papel em detrimento da função erétil. A redução desta citocina pode fornecer uma estratégia alternativa no tratamento da DE.
Title in English
Role of tumor necrosis factor alpha (TNF-a) in the pathophysiology of erectile dysfunction
Keywords in English
Cytokines
Heart disease
Necrosis
Nitric oxide
Penis
Abstract in English
Erectile dysfunction (ED) has been linked to cardiovascular diseases (CVD), which are associated with endothelial dysfunction and increased levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-a). We hypothesized that TNF-a impairs corpus cavernosum (CC) reactivity, which favors ED. The CC of TNF-a-infused animals displayed: 1) decreased non-adrenergic non-cholinergic (NANC)-mediated relaxation; 2) increased sympathetic nerve-mediated contraction; 3) decreased endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) gene expression. The CC of TNF-a knockout animals displayed increased endothelium-dependent and NANC-mediated relaxation as well as increased eNOS and nNOS expression. Contractile responses mediated by sympathetic nerves were decreased in the CC of TNF-a knockout animals. In summary, the present study shows that TNF-a plays a detrimental role in erectile function. Strategies that aim to reduce the levels of this cytokine may represent an alternative approach for ED treatment.
 
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Publishing Date
2011-08-24
 
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