RGD Reference Report - The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats. - Rat Genome Database

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The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats.

Authors: Ahn, GJ  Sohn, YS  Kang, KK  Ahn, BO  Kwon, JW  Kang, SK  Lee, BC  Hwang, WS 
Citation: Ahn GJ, etal., Int J Impot Res. 2005 Mar-Apr;17(2):134-41.
RGD ID: 2314521
Pubmed: PMID:15578039   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.ijir.3901295   (Journal Full-text)

The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor, DA-8159, on erectile function throughout the quantitative analysis of vascular endothelial cell, smooth muscle (SM), TGF-beta1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 (0, 5, 10, 20 mg/kg) was administered orally once a day to diabetic rats. After 8 weeks, immunohistochemistry and computerized image analysis were performed to quantify the percent area within the Corpora Cavernosa occupied by the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure (MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic rats showed a significant decrease in the SM and endothelial cell content, and an increase in the TGF-beta1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-beta1 expression level were 9.7+/-0.7, 4.5+/-0.7 and 17.9+/-2.1%, respectively. DA-8159 prevented reduction of SM (12.3+/-0.4% (5 mg/kg), 13.8+/-0.4% (20 mg/kg)) and endothelial cell content (5.6+/-0.5% (5 mg/kg), 6.3+/-0.6% (20 mg/kg)). Immunoreactivity of TGF-beta1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8+/-1.2% (5 mg/kg), 9.5+/-1.1% (20 mg/kg)). Electrostimulation of the cavernous nerve induced significant increase in maximum ICP (62.2+/-13.6 mmHg in 10 mg/kg vs 37.5+/-17.5 mmHg in diabetic group) and area under the curve of the ratio of ICP/MAP (8891.09+/-1957 in 10 mg/kg vs 6315.87+/-2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDE5AHumanimpotence  ISOPde5a (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
Pde5aRatimpotence  IMP associated with Diabetes Mellitus and ExperimentalRGD 
Pde5aMouseimpotence  ISOPde5a (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Pde5a  (phosphodiesterase 5A)

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

Genes (Homo sapiens)
PDE5A  (phosphodiesterase 5A)


Additional Information