RGD Reference Report - Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat. - Rat Genome Database

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Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat.

Authors: Ferrini, MG  Kovanecz, I  Sanchez, S  Vernet, D  Davila, HH  Rajfer, J  Gonzalez-Cadavid, NF 
Citation: Ferrini MG, etal., Biol Reprod. 2007 May;76(5):915-23. Epub 2007 Feb 7.
RGD ID: 2314469
Pubmed: PMID:17287493   (View Abstract at PubMed)
DOI: DOI:10.1095/biolreprod.106.059642   (Journal Full-text)

Aging-related erectile dysfunction is characterized by a loss of smooth muscle cells (SMCs) and fibrosis in the corpora cavernosa, and functionally by corporal veno-occlusive dysfunction (CVOD). Phosphodiesterase 5 (PDE5A) inhibitors, in part via upregulating inducible nitric oxide synthase (NOS2A), have antifibrotic properties in penile tissues. We aimed to determine whether in the aged rat the chronic long-term treatment with sildenafil ameliorates corporal SMC loss and fibrosis, stimulates NOS2A induction, and corrects the associated CVOD. Aged male rats (20 mo old) received sildenafil in their drinking water (20 mg/kg per day) or plain water for 45 days, and untreated young rats (5 mo old) served as controls (n = 8 per group). CVOD was assessed by dynamic infusion cavernosometry (DIC). Collagen:SMC (Masson trichrome) and collagen III:I (picrosirius red) ratios, SMC content (alpha-smooth muscle actin [ACTA2]), cell proliferation (proliferating nuclear antigen [PCNA]), apoptotic death (TUNEL), and NOS2A induction were measured by histochemistry and immunohistochemistry followed by quantitative image analysis. Collagen content was determined by hydroxyproline assay, and transforming growth factor beta-1 (TGFB1); xanthine oxidoreductase (XDH); ACTA2; NOS2A; and the Rho kinase inhibitor protein tyrosine phosphatase, nonreceptor type 11 (PTPN11), and activator, VAV, were measured by quantitative Western blot. In the aged rats treated with sildenafil, the erectile response by DIC was normalized, and the corporal SMC:collagen ratio and SMC number were increased. In addition, sildenafil reduced the corporal collagen content without affecting the collagen III:I ratio, increased the PCNA:apoptosis ratio, and stimulated NOS2A induction, although there was no effect on XDH, TGFB1, PTPN11, or VAV levels. These data show that long-term PDE5A treatment corrected CVOD in the aged rat and partially reversed the aging-related fibrosis and loss of SMC in the corpora cavernosa without affecting TGFB1 or PTPN11 levels, which are markers of oxidative stress. It may be speculated that similar effects may be achieved with this paradigm in men.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDE5AHumanvasculogenic impotence  ISOPde5a (Rattus norvegicus) RGD 
Pde5aRatvasculogenic impotence  IMP  RGD 
Pde5aMousevasculogenic impotence  ISOPde5a (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pde5a  (phosphodiesterase 5A)

Genes (Mus musculus)
Pde5a  (phosphodiesterase 5A, cGMP-specific)

Genes (Homo sapiens)
PDE5A  (phosphodiesterase 5A)


Additional Information