Effect of a phosphodiesterase-5A (PDE5A) gene polymorphism on response to sildenafil therapy in canine pulmonary hypertension.
Sci Rep
; 9(1): 6899, 2019 05 03.
Article
em En
| MEDLINE
| ID: mdl-31053768
ABSTRACT
Pulmonary hypertension (PH) is a common clinical condition associated with morbidity and mortality in both humans and dogs. Sildenafil, a phosphodiesterase-5 (PDE5) inhibitor causing accumulation of cGMP, is frequently used for treatment of PH. The authors previously reported a PDE5AE90K polymorphism in dogs that results in lower basal cyclic guanosine monophosphate (cGMP) concentrations than in wild-type dogs, which could contribute to variability in the efficacy of sildenafil. In this study, response to sildenafil therapy was evaluated in dogs with PH by comparing echocardiographic parameters, quality-of-life (QOL) score, and plasma cGMP concentrations before and after sildenafil therapy. Overall, tricuspid regurgitation estimated systolic pressure gradient (PG) and QOL score were significantly improved after sildenafil therapy, and the plasma cGMP concentration was significantly decreased. Dogs that had a heterozygous PDE5A status had a significantly worse QOL score when compared to the wildtype group after sildenafil treatment. The simple and multiple regression analyses revealed a significant but weak prediction for the percent reduction in QOL score with sildenafil treatment by plasma cGMP level and by the PDE5AE90K polymorphic status. This study showed that sildenafil treatment improved PH in dogs, and the PDE5AE90K polymorphism blunted the efficacy of sildenafil in terms of QOL improvement.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
/
Nucleotídeo Cíclico Fosfodiesterase do Tipo 5
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Citrato de Sildenafila
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Hipertensão Pulmonar
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos