Activation of the ET-1/ETA pathway contributes to erectile dysfunction associated with mineralocorticoid hypertension.
dc.contributor.author | Carneiro, Fernando Silva | |
dc.contributor.author | Nunes, Kenia Pedrosa | |
dc.contributor.author | Vitorino, Fernanda Regina Casagrande Giachini | |
dc.contributor.author | Lima, Victor Vitorino | |
dc.contributor.author | Carneiro, Zidonia N. | |
dc.contributor.author | Nogueira, Edson F. | |
dc.contributor.author | Leite, Romulo | |
dc.contributor.author | Ergul, Adviye | |
dc.contributor.author | Rainey, William E. | |
dc.contributor.author | Webb, Robert Clinton | |
dc.contributor.author | Passaglia, Rita de Cassia Aleixo Tostes | |
dc.date.accessioned | 2017-03-29T16:46:02Z | |
dc.date.available | 2017-03-29T16:46:02Z | |
dc.date.issued | 2008 | |
dc.description.abstract | Introduction. 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. | pt_BR |
dc.identifier.citation | CARNEIRO, F. S. et. al. Activation of the ET-1/ETA pathway contributes to erectile dysfunction associated with mineralocorticoid hypertension. The Journal of Sexual Medicine, v. 5, p. 2793-2807, 2008. Disponível em: <http://onlinelibrary.wiley.com/doi/10.1111/j.1743-6109.2008.01009.x/abstract>. Acesso em: 10 jan. 2017. | pt_BR |
dc.identifier.doi | https://doi.org/10.1111/j.1743-6109.2008.01009.x | |
dc.identifier.issn | 1743-6095 | |
dc.identifier.uri | http://www.repositorio.ufop.br/handle/123456789/7483 | |
dc.identifier.uri2 | http://onlinelibrary.wiley.com/doi/10.1111/j.1743-6109.2008.01009.x/abstract | pt_BR |
dc.language.iso | en_US | pt_BR |
dc.rights | restrito | pt_BR |
dc.subject | Rho-kinase | pt_BR |
dc.subject | Corpus Cavernosum | pt_BR |
dc.subject | Atrasentan | pt_BR |
dc.title | Activation of the ET-1/ETA pathway contributes to erectile dysfunction associated with mineralocorticoid hypertension. | pt_BR |
dc.type | Artigo publicado em periodico | pt_BR |