title: Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat.
abstract: OBJECTIVE
  Impotence, specifically corporal veno-occlusive dysfunction (CVOD), occurs after radical prostatectomy. It results from the effects of cavernosal nerve damage, which causes smooth muscle (SM) loss and an increase in collagen within the corpora. Recent reports have suggested that long-term treatment with phosphodiesterase-5 inhibitors after radical prostatectomy may prevent such changes. We aimed to determine whether bilateral cavernosal nerve resection (BCNX) in the rat leads to CVOD and whether long-term phosphodiesterase-5 inhibition ameliorates these histologic and functional impairments.
  
  
  METHODS
  Rats (n = 7 to 11/group) underwent either the sham operation, BCNX, or BCNX plus 30 mg/L vardenafil in the drinking water. Before the rats were killed 45 days later, CVOD was assessed by dynamic infusion cavernosometry. The corpora underwent histochemistry/immunohistochemistry with quantitative image analysis for SM/collagen ratio, collagen III/I ratio, alpha-SM actin, inducible nitric oxide synthase (iNOS), proliferating cell nuclear antigen, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling as a marker of apoptosis.
  
  
  RESULTS
  Compared with the sham group, the BCNX rats demonstrated CVOD as measured by the drop rate, a 60% reduction in the SM/collagen ratio, a twofold increase in iNOS expression, and a threefold increase in intracorporeal apoptosis. Compared with the BCNX group, vardenafil increased both iNOS and proliferating cell nuclear antigen expression (SM cell replication), with normalization of the dynamic infusion cavernosometry drop rate and SM/collagen ratio.
  
  
  CONCLUSIONS
  Long-term treatment with vardenafil may prevent CVOD after radical prostatectomy by preserving SM content and inhibiting corporal fibrosis possibly by its effect on iNOS.
authors.affiliation: Department of Urology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA. mferrrini@labiomed.org
authors.forename: Monica G
authors.initials: MG
authors.lastname: Ferrini
authors.forename: Hugo H
authors.initials: HH
authors.lastname: Davila
authors.forename: Istvan
authors.initials: I
authors.lastname: Kovanecz
authors.forename: Sandra P
authors.initials: SP
authors.lastname: Sanchez
authors.forename: Nestor F
authors.initials: NF
authors.lastname: Gonzalez-Cadavid
authors.forename: Jacob
authors.initials: J
authors.lastname: Rajfer
mesh_terms: D000818:Animals; D003714:Denervation / Q000379:methods; D005355:Fibrosis; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D009130:Muscle, Smooth; D010413:Penis / Q000098:blood supply / Q000294:innervation* / Q000473:pathology*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D013450:Sulfones / Q000627:therapeutic use; D014227:Triazines / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride; D014652:Vascular Diseases / Q000517:prevention & control*
chemical_list: D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride