title: Cavernous neurotomy in the rat is associated with the onset of an overt condition of hypogonadism.
abstract: BACKGROUND
  Most men following radical retropubic prostatectomy (RRP) are afflicted by erectile dysfunction (ED). RRP-related ED occurs as a result of surgically elicited neuropraxia, leading to histological changes in the penis, including collagenization of smooth muscle and endothelial damage.
  
  
  OBJECTIVE
  To verify whether hypogonadism could contribute to the pathogenesis of RRP-ED.
  
  
  METHODS
  Effects of testosterone (T), alone or in association with long-term tadalafil (Tad) treatment in a rat model of bilateral cavernous neurotomy (BCN).
  
  
  METHODS
  Penile tissues from rats were harvested for vasoreactivity studies 3 months post-BCN. Penile oxygenation was evaluated by hypoxyprobe immunostaining. Phosphodiesterase type 5 (PDE5), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expression were quantified by Real Time quantitative reverse transcription polymerase chain reaction (qRT-PCR).
  
  
  RESULTS
  In BCN rats, we observed the onset of an overt condition of hypogonadism, characterized by reduced T plasma level, reduced ventral prostate weight, reduced testis function (including testis weight and number of Leydig cells), with an inadequate compensatory increase of luteinizing hormone. BCN induced massive penile hypoxia, decreased muscle/fiber ratio, nNOS, eNOS, PDE5 expression, increased sensitivity to the nitric oxide donor, sodium nitroprusside (SNP), and reduced the relaxant response to acetylcholine (Ach), as well as unresponsiveness to acute Tad dosing. In BCN rats, chronic Tad-administration normalizes penile oxygenation, smooth muscle loss, PDE5 expression, SNP sensitivity, and the responsiveness to the acute Tad administration. Chronic Tad treatment was ineffective in counteracting the reduction of nNOS and eNOS expression, along with Ach responsiveness. T supplementation, in combination with Tad, reverted some of the aforementioned alterations, restoring smooth muscle content, eNOS expression, as well as the relaxant response of penile strips to Ach, but not nNOS expression.
  
  
  CONCLUSIONS
  BCN was associated with hypogonadism, probably of central origin. T supplementation in hypogonadal BCN rats ameliorates some aspects of BCN-induced ED, including collagenization of penile smooth muscle and endothelial dysfunction, except surgically induced altered nNOS expression.
authors.affiliation: Andrology Unit Department of Clinical Physiopathology, University of Florence, Florence 50139, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Vignozzi
authors.forename: Sandra
authors.initials: S
authors.lastname: Filippi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Morelli
authors.forename: Mirca
authors.initials: M
authors.lastname: Marini
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chavalmane
authors.forename: Benedetta
authors.initials: B
authors.lastname: Fibbi
authors.forename: Enrico
authors.initials: E
authors.lastname: Silvestrini
authors.forename: Rosa
authors.initials: R
authors.lastname: Mancina
authors.forename: Marco
authors.initials: M
authors.lastname: Carini
authors.forename: G Barbara
authors.initials: GB
authors.lastname: Vannelli
authors.forename: Gianni
authors.initials: G
authors.lastname: Forti
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
mesh_terms: D000818:Animals; D002243:Carbolines / Q000008:administration & dosage; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000209:etiology*; D006801:Humans; D007006:Hypogonadism / Q000209:etiology*; D066298:In Vitro Techniques; D008297:Male; D010413:Penis / Q000294:innervation* / Q000502:physiology / Q000601:surgery; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage; D011468:Prostatectomy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068581:Tadalafil
chemical_list: D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil