Sildenafil is the most used treatment of erectile dysfunction, however a large part of patients do not respond to therapy. This drug enhances nitric oxide (NO) signaling, and therefore factors that alter NO production may impact this drug responsiveness. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of all NO synthases, and is metabolized by Dimethylarginine Dimethilaminohydrolase (DDAH) 1 and 2. Here we aimed to assess the relationship between plasma levels of ADMA and nitrite (marker of nitric oxide production) with Sildenafil responsiveness. We also studied genetic polymorphisms in DDAH1 and DDAH2 genes and their relation with biochemical and clinical data. Were included here 140 patients, divided in Clinical Erectile Dysfunction (CED) or Post-Prostatectomy Erectile Dysfunction (PPED) groups. Erectile function was evaluated before and after Sildenafil on-demand treatment using the International Index for Erectile Function Questionnaire. We have found that nitrite was associated with worse response to Sildenafil (r = - 0.25, P = 0.040). rs1554597 and rs18582 DDAH1 polymorphisms were associated with changes in ADMA levels in CED (B = - 0.23, P = 0.002; B = - 0.15, P = 0.017 for both variant genotypes, respectively). Finally, DDAH2 polymorphisms were associated with altered responsiveness to Sildenafil in PPED (B = +0.19, P = 0.027).
Nitric oxide : biology and chemistry. 2017 Oct 23 [Epub ahead of print]
Ana Maria Milanez Azevedo, Guilhermo Brites-Anselmi, Lucas Cezar Pinheiro, Vanessa de Almeida Belo, Fernanda Borchers Coeli-Lacchini, Carlos Augusto Fernandes Molina, Murilo Ferreira de Andrade, Silvio Tucci, Emilio Hirsch, Jose Eduardo Tanus-Santos, Riccardo Lacchini
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil., Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of Sao Paulo, Brazil., Department of General Biology, Biological Sciences Institute, Federal University of Minas Gerais, Brazil., Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Brazil., Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Brazil., Department of Molecular Biotechnology and Health Sciences, University of Torino, Italy., Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of Sao Paulo, Brazil. Electronic address: .