Erectile Dysfunction in Wistar Audiogenic Rats Is Associated With Increased Cavernosal Contraction and Decreased Neuronal Nitric Oxide Synthase Protein Expression

Autor(es)

Rodrigues, Fernanda Luciano ; Fais, Rafael S. ; Pereira, Marlia G. A. G. ; Garcia-Cairasco, Norberto ; Tostes, Rita C. ; Carneiro, Fernando S.

• Tipo de documento: Artigo Científico
• Fonte: UROLOGY; v. 106, AUG 2017.
• Citações Web of Science: 0

Resumo

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. (C) 2017 Elsevier Inc. (AU)

• Processo FAPESP: 10/17362-4 - Mecanismos da disfunção erétil na insuficiência cardíaca
• Beneficiário: Fernando Silva Carneiro
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/21976-1 - Controle autonômico cardiovascular em camundongos knockout para receptores toll-like 9 com hipertensão induzida por angiotensina II.
• Beneficiário: Fernanda Luciano Rodrigues
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 07/50261-4 - Neurociências, epilepsia e arte: caracterização interdisciplinar da cepa WAR e modelos de epilepsia correlacionados: as oficinas Da Vinci, divulgação científica e quebras de estigmas em epilepsia
• Beneficiário: Norberto Garcia Cairasco
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 05/56447-7 - Pesquisa através de imagens por ressonância magnética de alto campo destinadas a estudos em humanos
• Beneficiário: João Pereira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Programa CINAPCE - Temático
• Processo FAPESP: 16/11988-5 - Contribuição do NLRP3 para o efeito pró-inflamatório da ET-1 em células de músculo liso do corpo cavernoso: relevância na função erétil.
• Beneficiário: Fernando Silva Carneiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular