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Phosphodiesterase-9 (PDE9) inhibition with BAY 73-6691 increases corpus cavernosum relaxations mediated by nitric oxide-cyclic GMP pathway in mice.
MedLine Citation:
PMID:  23034509     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Phosphodiesterase-9 (PDE9) specifically hydrolyzes cyclic GMP, and was detected in human corpus cavernosum. However, no previous studies explored the selective PDE9 inhibition with BAY 73-6691 in corpus cavernosum relaxations. Therefore, this study aimed to characterize the PDE9 mRNA expression in mice corpus cavernosum, and investigate the effects of BAY 73-6691 in endothelium-dependent and -independent relaxations, along with the nitrergic corpus cavernosum relaxations. Male mice received daily gavage of BAY 73-6691 (or dimethylsulfoxide) at 3 mg kg(-1) per day for 21 days. Relaxant responses to acetylcholine (ACh), nitric oxide (NO) (as acidified sodium nitrite; NaNO(2) solution), sildenafil and electrical-field stimulation (EFS) were obtained in corpus cavernosum in control and BAY 73-6691-treated mice. BAY 73-6691 was also added in vitro 30 min before construction of concentration-responses and frequency curves. PDE9A and PDE5 mRNA expression was detected in the mice corpus cavernosum in a similar manner. In vitro addition of BAY 73-6691 neither itself relaxed mice corpus cavernosum nor changed the NaNO(2), sildenafil and EFS-induced relaxations. However, in mice treated chronically with BAY 73-6691, the potency (pEC(50)) values for ACh, NaNO(2) and sildenafil were significantly greater compared with control group. The maximal responses (E(max)) to NaNO(2) and sildenafil were also significantly greater in BAY 73-6691-treated mice. BAY 73-6691 treatment also significantly increased the magnitude and duration of the nitrergic corpus cavernosum relaxations (8-32 Hz). In conclusion, murine corpus cavernosum expresses PDE9 mRNA. Prolonged PDE9 inhibition with BAY 73-6691 amplifies the NO-cGMP-mediated cavernosal responses, and may be of therapeutic value for erectile dysfunction.International Journal of Impotence Research advance online publication, 4 October 2012; doi:10.1038/ijir.2012.35.
Authors:
F H da Silva; M N Pereira; C F Franco-Penteado; G De Nucci; E Antunes; M A Claudino
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-04
Journal Detail:
Title:  International journal of impotence research     Volume:  -     ISSN:  1476-5489     ISO Abbreviation:  Int. J. Impot. Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007383     Medline TA:  Int J Impot Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP) Campinas, São Paulo, Brazil.
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