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Pharmacol Rep ; 69(3): 532-535, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28363184

RESUMO

BACKGROUND: Recent studies reveal that nerve growth factor (NGF) plays a critical role in the pathobiology of pulmonary hypertension (PH). The aim of the present study is to clarify the relationship between NGF signaling and treatment with PDGF or ROCK inhibitors in an animal model of PH. METHODS: Lung tissues were obtained from animals with monocrotaline (MCT)-challenged PH which had been administered long term imatinib, fasudil or statin. Reversal of disease was indicated by decreases in right ventricle pressure (RVP) and hypertrophy. NGF expression was examined at the mRNA and protein levels using quantitative real-time PCR reaction and ELISA. RESULTS: MCT significantly increased NGF mRNA and protein content in lung tissue. ROCK inhibitor (fasudil) and PDGF inhibitor (imatinib) caused significant decreases in NGF mRNA and protein content when administered alone, with no further effects noted when used in combination. CONCLUSION: The beneficial reversal of MCT-mediated effects in PH caused by PDGF or ROCK inhibition may be also partially mediated by decreased NGF signaling.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Quinases Associadas a rho/antagonistas & inibidores , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertensão Pulmonar/fisiopatologia , Mesilato de Imatinib/farmacologia , Masculino , Monocrotalina/farmacologia , Fator de Crescimento Neural/genética , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos
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