Activation of the ET-1/ETA pathway contributes to erectile dysfunction associated with mineralocorticoid hypertension.

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Autor(es): dc.creatorCarneiro, Fernando Silva-
Autor(es): dc.creatorNunes, Kenia Pedrosa-
Autor(es): dc.creatorVitorino, Fernanda Regina Casagrande Giachini-
Autor(es): dc.creatorLima, Victor Vitorino-
Autor(es): dc.creatorCarneiro, Zidonia N.-
Autor(es): dc.creatorNogueira, Edson F.-
Autor(es): dc.creatorLeite, Romulo-
Autor(es): dc.creatorErgul, Adviye-
Autor(es): dc.creatorRainey, William E.-
Autor(es): dc.creatorWebb, Robert Clinton-
Autor(es): dc.creatorPassaglia, Rita de Cassia Aleixo Tostes-
Data de aceite: dc.date.accessioned2025-08-21T15:58:12Z-
Data de disponibilização: dc.date.available2025-08-21T15:58:12Z-
Data de envio: dc.date.issued2017-03-29-
Data de envio: dc.date.issued2017-03-29-
Data de envio: dc.date.issued2008-
Fonte completa do material: dc.identifierhttp://www.repositorio.ufop.br/handle/123456789/7483-
Fonte completa do material: dc.identifierhttp://onlinelibrary.wiley.com/doi/10.1111/j.1743-6109.2008.01009.x/abstract-
Fonte completa do material: dc.identifierhttps://doi.org/10.1111/j.1743-6109.2008.01009.x-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/1028864-
Descrição: dc.descriptionIntroduction. The cavernosal tissue is highly responsive to endothelin-1 (ET-1), and penile smooth muscle cells not only respond to but also synthesize ET-1. Aim. Considering that ET-1 is directly involved in end-organ damage in salt-sensitive forms of hypertension, we hypothesized that activation of the ET-1/ETA receptor pathway contributes to erectile dysfunction (ED) associated with mineralocorticoid hypertension. Methods. Wistar rats were uninephrectomized and submitted to deoxycorticosterone acetate (DOCA)-salt treatment for 5 weeks. Control (Uni [uninephrectomized control]) animals were uninephrectomized and given tap water. Uni and DOCA-salt rats were simultaneously treated with vehicle or atrasentan (ETA receptor antagonist, 5 mg/ Kg/day). Cavernosal reactivity to ET-1, phenylephrine (PE), ETB receptor agonist (IRL-1620) and electric field stimulation (EFS) were evaluated in vitro. Expression of ROCKa, ROCKb, myosin phosphatase target subunit 1 (MYPT-1), and extracellular signal-regulated kinase 1/2 (ERK 1/2) were evaluated by western blot analysis. ET-1 and ETA receptor mRNA expression was evaluated by real-time reverse-transcriptase polymerase chain reaction. Voltage-dependent increase in intracavernosal pressure/mean arterial pressure (ICP/MAP) was used to evaluate erectile function in vivo. Main Outcome Measure. ETA receptor blockade prevents DOCA-salt-associated ED. Results. Cavernosal strips from DOCA-salt rats displayed augmented preproET-1 expression, increased contractile responses to ET-1 and decreased relaxation to IRL-1620. Contractile responses induced by EFS and PE were enhanced in cavernosal tissues from DOCA-salt hypertensive rats. These functional changes were associated with increased activation of the RhoA/Rho-kinase and ERK 1/2 pathways. Treatment of rats with atrasentan completely prevented changes in cavernosal reactivity in DOCA-salt rats and restored the decreased ICP/MAP, completely preventing ED in DOCA-salt rats. Conclusion. Activation of the ET-1/ETA pathway contributes to mineralocorticoid hypertension-associated ED. ETA receptor blockade may represent an alternative therapeutic approach for ED associated with salt-sensitive hypertension and in pathological conditions where increased levels of ET-1 are present.-
Formato: dc.formatapplication/pdf-
Idioma: dc.languageen-
Direitos: dc.rightsrestrito-
Palavras-chave: dc.subjectRho-kinase-
Palavras-chave: dc.subjectCorpus Cavernosum-
Palavras-chave: dc.subjectAtrasentan-
Título: dc.titleActivation of the ET-1/ETA pathway contributes to erectile dysfunction associated with mineralocorticoid hypertension.-
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