title: Nitrergic function is lost but endothelial function is preserved in the corpus cavernosum and penile resistance arteries of men after radical prostatectomy.
abstract: BACKGROUND
  Radical prostatectomy (RP) frequently results in erectile dysfunction (ED). It has been hypothesized that alterations of cavernosal tissue subsequent to RP contribute to ED but functional evaluation of the impact of RP on human erectile structures is lacking.
  
  
  OBJECTIVE
  This study aims to evaluate endothelial function of human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) and neurogenic responses of HCC from patients with ED secondary to RP (ED-RP).
  
  
  METHODS
  HCC strips and HPRA were obtained from organ donors without history of ED (No-ED) and patients with ED who were segregated depending on ED etiology: ED-RP or vasculogenic (ED-VASC). Functional evaluation of HCC and HPRA was performed in organ chambers and wire myographs, respectively. Histological evaluation of cavernosal tissue consisted of trichrome staining for fibrosis quantification and TUNEL assay for determination of apoptosis.
  
  
  METHODS
  Endothelium-dependent and endothelium-independent relaxation, electrical field stimulation (EFS)-induced neurogenic contraction and relaxation, and cavernosal fibrosis and apoptosis.
  
  
  RESULTS
  Endothelium-dependent relaxations were significantly impaired in HCC and HPRA from ED-VASC patients while these responses in ED-PR patients were not different to No-ED. Similarly, sildenafil-induced relaxations were reduced in HCC and HPRA from ED-VASC but were preserved in ED-RP. Adrenergic contractions induced by EFS in HCC were potentiated in both ED-RP and ED-VASC. EFS-induced nitrergic relaxation was significantly reduced in HCC from ED-VASC but was almost abolished in ED-RP. Fibrous tissue content and cavernosal apoptosis in HCC from ED-RP were not significantly different from No-ED.
  
  
  CONCLUSIONS
  Endothelial function and cavernosal sensitivity to phosphodiesterase type 5 inhibitors are preserved in erectile tissue from ED-RP while a marked imbalance in neurogenic modulation of cavernosal tone favoring adrenergic contractile responses over nitrergic relaxation is manifested. Fibrotic and apoptotic processes in cavernosal tissue are not specifically associated to ED-RP. These evidences could help to retarget therapeutic strategies in the management of ED after RP.
authors.affiliation: Servicio de Urología, Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Martínez-Salamanca
authors.forename: José M
authors.initials: JM
authors.lastname: La Fuente
authors.forename: Argentina
authors.initials: A
authors.lastname: Fernández
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez-Salamanca
authors.forename: Augusto J
authors.initials: AJ
authors.lastname: Pepe-Cardoso
authors.forename: Joaquín
authors.initials: J
authors.lastname: Carballido
authors.forename: Javier
authors.initials: J
authors.lastname: Angulo
mesh_terms: D017209:Apoptosis; D004727:Endothelium / Q000378:metabolism; D007172:Erectile Dysfunction / Q000209:etiology* / Q000503:physiopathology*; D005355:Fibrosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000098:blood supply* / Q000294:innervation*; D011468:Prostatectomy / Q000009:adverse effects*; D014664:Vasodilation
chemical_list: D009569:Nitric Oxide
keywords: Endothelium-Dependent Relaxation; Erectile Dysfunction; Human Corpus Cavernosum; Nitrergic Relaxation; Penile Rehabilitation; Radical Prostatectomy