Erectile dysfunction in heart failure rats is associated with increased neurogenic contractions in cavernous tissue and internal pudendal artery

Autor(es)

Rodrigues, Fernanda Luciano ^[1] ; Lopes, Rheure Alves M. ^[1] ; Fais, Rafael Sobrano ^[1] ; de Oliveira, Lucas ^[1] ; Prado, Cibele M. ^[2] ; Tostes, Rita C. ^[1] ; Carneiro, Fernando S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Med Sch, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Pathol & Legal Med, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 145, p. 9-18, JAN 15 2016.
• Citações Web of Science: 3

Resumo

Aims: The rates of erectile dysfunction (ED) in heart failure (HF) are extremely high. This study tested the hypothesis that rats with HF display ED and that HF leads to increased sympathetic-mediated contractile tone of the cavernous tissue and/or internal pudendal arteries (IPA) as potential mechanisms contributing to ED. Main methods: HF was induced in Wistar rats by ligation of the left anterior descending coronary artery. Changes in the ratio of intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of major pelvic ganglion were determined in vivo. Cavernosal and IPA contractions were induced by electric field stimulation (EFS) and phenylephrine. RhoA, Rho kinase 2 (ROCK 2) and myosin phosphatase target protein 1 (MYPT-1) protein expression and phosphorylation levels were also determined. Key findings: HF rats display impaired erectile function represented by decreased ICP/MAP responses. EFS-mediated contractions were increased by HF in cavernous tissue and IPA. Contractions induced by phenylephrine were increased in cavernous tissue of HF rats, but decreased in IPA rings. Moreover, HF decreased RhoA protein expression, but increased ROCK 2 and MYPT-1 phosphorylation levels in cavernous tissue. In conclusion, rats with HF induced by myocardial infarction display ED in vivo and increased sympathetic-mediated contractile responses in cavernous tissue and IPA. Increased sympathetic-mediated contractile responses were associated with increased ROCK 2 and MYPT-1 phosphorylation in cavernosal tissue, suggesting the involvement of ROCK signaling pathway in ED genesis. Significance: Our findings suggest new mechanisms linking HF to ED, providing potential therapeutic targets for treating ED associated to HF. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 10/17362-4 - Mecanismos da disfunção erétil na insuficiência cardíaca
• Beneficiário: Fernando Silva Carneiro
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores