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Functional and structural changes in internal pudendal arteries underlie erectile dysfunction induced by androgen deprivation

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Asian Journal of Andrology 2017年第5期19卷 526-532页

作者： Rheure Alves-Lopes Karla B Neves Marcondes AB Silva Vania C Olivon Silvia G Ruginsk Jose Antunes-Rodrigues leandra nz ramalho Rita C Tostes Fernando Silva Carneiro Department of Pharmacology Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto SP Brazil Department of Physics and Chemistry Faculty of Pharmaceutical Sciences of Ribeirao Preto University of Sao Paulo Ribeirao Preto SP Brazil Department of Physiological Sciences Biomedical Sciences InstituteFederal University of Alfenas Alfenas MG Brazil Department of Physiology Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto SP Brazil Department of Pathology and Legal Medicine Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto SP Brazil

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/ryr182） 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.

关键词： androgen castration internal pudendal artery

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