Caracterização dos efeitos de Dioclea grandiflora Martius ex Bentham sobre a função cardiovascular de ratos com hipertensão pulmonar induzida por monocrotalina

• Ano de defesa: 2019
• Autor(a) principal: Maciel, Priscilla Maria Pereira
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal da Paraíba; Brasil; Farmacologia; Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos; UFPB
• Palavras-chave em Português: Dioclea grandiflora; Função vascular pulmonar; Atividade antioxidante; Hipertensão pulmonar; Monocrotalina; Pulmonary vascular function; Antioxidant activity; Pulmonary hypertension; Monocrotaline; CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
• Link de acesso: https://repositorio.ufpb.br/jspui/handle/123456789/18792

Pulmonary hypertension (HP) is characterized by elevated pulmonary artery pressure (PAP) and right ventricular hypertrophy (RVH). Due to the heterogeneity of this disease and its progressive nature, the drugs established for its treatment become less effective in the long term. The aim of this study was to evaluate the effects of the hydroalcoholic extract of monocrotaline (MCT) –induced. Dioclea grandiflora (Dg) root bark in rats, in order to discover new candidates for HP treatment. The animals were divided into the groups: control (normotensive), hypertensive-MCT (HP-MCT), MCT hypertensive treated with Dg 12.5 (HP-Dg 12.5) and 37.5 mg/kg (HP-Dg 37,5), sildenafil-treated hypertensive-MCT (HP-Sild; 50 mg/kg), and hypertensive-MCT treated with the combination of sildenafil and Dg 37.5 mg/kg, which received intragastric treatment for 28 days after 24 hours of MCT administration. In the evaluation of the echocardiographic parameters, the HP-Dg 37.5 mg / kg and HP-Sild groups presented a lower delta pulmonary artery acceleration time and smaller measurements of RV wall thickness and diastolic diameter in relation to the HP- MCT. In the right ventricular systolic pressure (RVSP) direct measurement, the HP-MCT group presented significantly higher pressure levels than the CTL group. Treatments isolated with Dg (37.5 mg/kg) and sildenafil, or combined treatment significantly reduced RVSP values when compared to the HP-MCT group. Right ventricular hypertrophy (RVH) was partially prevented in the HP-Dg 37.5, HP-Sild and HP-COMB groups, which was accompanied by an improvement in right ventricular systolic and diastolic function. In the vascular reactivity assays, no significant differences were observed in the vasoconstricting responses to phenylephrine between the groups. Treatment with Dg did not reverse the impaired response to vasodilator agents, acetylcholine (ACh) and sodium nitroprusside (NPS) when compared to the HP-MCT group. In the HP-Sild and HP-COMB groups the response to ACh was restored, however this effect was not observed for NPS. HP-Dg (37.5 mg/kg), HP-Sild and HP-COMB groups had lower pulmonary vascular wall thickening as well as reduced levels of superoxide anions compared to the HP-MCT group. For these groups, less infiltration of inflammatory cells into lung tissue was also observed. These results demonstrate that treatment with Dg was effective in preventing the increase of PSVD and HVD, as well as preserving ventricular function by improving MCT-induced HP. Reduction of RVSP may be associated with a reduction of hypertrophic remodeling of pulmonary vessels and vascular oxidative stress, and reduction of inflammation.