title: Effect of chronic tadalafil administration on penile hypoxia induced by cavernous neurotomy in the rat.
abstract: BACKGROUND
  Numerous men develop postprostatectomy erectile dysfunction (PPED), due to surgery-related nervous damage. PPED is often refractory to phosphodiesterase type 5 (PDE5) inhibitors therapy.
  
  
  OBJECTIVE
  To verify whether chronic tadalafil (CT) preserves bilateral cavernous neurotomy (BCN)-induced penile damage and hypo-oxygenation.
  
  
  METHODS
  In a rat model of BCN we evaluated in vitro and ex vivo effect of CT treatment (2 mg/kg, daily for 3 months).
  
  
  RESULTS
  Bilateral cavernous neurotomy induced massive hypoxia and decreased muscle/fiber ratio, completely restored by CT. Hypersensitivity of hypoxic tissues to the relaxant effect of the endothelin type B receptor (ETB) agonist IRL-1620 was observed, along with ETB mRNA and protein overexpression. CT restored sensitivity to IRL-1620, and normalized ETB expression. Hypoxic penis showed increased sensitivity to the relaxant effect of the nitric oxide donor sodium nitroprusside (SNP), while acute tadalafil (100 nM) did not amplify the SNP effect. Accordingly, PDE5 mRNA and protein were reduced in BCN penile tissues. By restoring PDE5, CT decreased SNP-induced relaxation and rescued sensitivity to acute tadalafil. However, in hypoxic penis, CT normalizes neither acetylcholine hyporesponsiveness nor neuronal nitric oxide synthase-endothelial nitric oxide synthase expression.
  
  
  CONCLUSIONS
  Chronic tadalafil restores some of the investigated BCN-induced alterations, including PDE5 and tadalafil efficacy.
authors: Andrology Unit, Department of Clinical Physiopathology, Center of Research, Transfer and High Education, University of Florence, Florence, Italy.
authors: Linda
authors: L
authors: Vignozzi
authors: Sandra
authors: S
authors: Filippi
authors: Annamaria
authors: A
authors: Morelli
authors: Stefano
authors: S
authors: Ambrosini
authors: Michaela
authors: M
authors: Luconi
authors: Gabriella Barbara
authors: GB
authors: Vannelli
authors: Silvia
authors: S
authors: Donati
authors: Clara
authors: C
authors: Crescioli
authors: Xin-Hua
authors: XH
authors: Zhang
authors: Vincenzo
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authors: Mirone
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