title: Functional and structural changes in internal pudendal arteries underlie erectile dysfunction induced by androgen deprivation.
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.
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Rh Ure
authors.initials: RU
authors.lastname: Alves-Lopes
authors.affiliation: 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.
authors.forename: Karla B
authors.initials: KB
authors.lastname: Neves
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Marcondes Ab
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Vânia C
authors.initials: VC
authors.lastname: Olivon
authors.affiliation: Department of Physiological Sciences, Biomedical Sciences Institute, Federal University of Alfenas, Alfenas, MG, Brazil.|Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Ruginsk
authors.affiliation: Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Antunes-Rodrigues
authors.affiliation: Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Leandra Nz
authors.initials: LN
authors.lastname: Ramalho
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Fernando Silva
authors.initials: FS
authors.lastname: Carneiro
mesh_terms: D000728:Androgens / Q000172:deficiency*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D062186:Arterial Pressure; D001158:Arteries / Q000473:pathology* / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009919:Orchiectomy; D010413:Penis / Q000098:blood supply / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000728:Androgens; D051017:Apoptosis Regulatory Proteins; D013739:Testosterone