Functional and structural changes in internal pudendal arteries underlie erectile dysfunction induced by androgen deprivation
Alves-Lopes, Rhéure and Neves, Karla B. and Silva, Marcondes A.B. and Olivon, Vânia C. and Ruginsk, Silvia G. and Antunes-Rodrigues, José and Ramalho, Leandra N.Z. and Tostes, Rita C. and Carneiro, Fernando Silva (2016) Functional and structural changes in internal pudendal arteries underlie erectile dysfunction induced by androgen deprivation. Asian Journal of Andrology, 19 (5). pp. 526-532. ISSN 1745-7262 (https://doi.org/10.4103/1008-682X.173935)
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Abstract
Androgen deficiency is strongly associated with erectile dysfunction (ED). Inadequate penile arterial blood flow is one of the major causes of ED. The blood flow to the corpus cavernosum is mainly derived from the internal pudendal arteries (IPAs); however, no study has evaluated the effects of androgen deprivation on IPA's function. We hypothesized that castration impairs IPAs reactivity and structure, contributing to ED. In our study, Wistar male rats, 8-week-old, were castrated and studied 30 days after orchiectomy. Functional and structural properties of rat IPAs were determined using wire and pressure myograph systems, respectively. Protein expression was determined by Western blot and immunohistochemistry. Plasma testosterone levels were determined using the IMMULITE 1000 Immunoassay System. Castrated rats exhibited impaired erectile function, represented by decreased intracavernosal pressure/mean arterial pressure ratio. IPAs from castrated rats exhibited decreased phenylephrine- and electrical field stimulation (EFS)-induced contraction and decreased acetylcholine- and EFS-induced vasodilatation. IPAs from castrated rats exhibited decreased internal diameter, external diameter, thickness of the arterial wall, and cross-sectional area. Castration decreased nNOS and α-actin expression and increased collagen expression, p38 (Thr180/Tyr182) phosphorylation, as well as caspase 3 cleavage. In conclusion, androgen deficiency is associated with impairment of IPA reactivity and structure and increased apoptosis signaling markers. Our findings suggest that androgen deficiency-induced vascular dysfunction is an event involving hypotrophic vascular remodeling of IPAs.
ORCID iDs
Alves-Lopes, Rhéure, Neves, Karla B. ORCID: https://orcid.org/0000-0001-5158-9263, Silva, Marcondes A.B., Olivon, Vânia C., Ruginsk, Silvia G., Antunes-Rodrigues, José, Ramalho, Leandra N.Z., Tostes, Rita C. and Carneiro, Fernando Silva;-
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Item type: Article ID code: 82729 Dates: DateEvent5 July 2016Published23 November 2015AcceptedNotes: Funding Information: This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-2010-17362-4 and 2011-23060-3), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Publisher Copyright: © 2016 AJA, SIMM & SJTU. All rights reserved. Subjects: Medicine Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 13 Oct 2022 08:02 Last modified: 17 Nov 2024 01:22 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/82729