Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2018
Trapidil improves hemodynamic, echocardiographic and redox state parameters of right ventricle in monocrotaline-induced pulmonary arterial hypertension model.
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Türck Patrick, Lacerda Denise Santos, Carraro Cristina Campos, de Lima-Seolin Bruna Gazzi, Teixeira Rayane Brinck, Poletto Bonetto Jéssica Hellen, Colombo Rafael, Schenkel Paulo Cavalheiro, Belló-Klein Adriane, da Rosa Araujo Alex Sander
Аннотация
BACKGROUND: Pulmonary arterial hypertension is a disease characterized by increased pulmonary vascular resistance and redox imbalance, leading to failure of right ventricle. Trapidil has been described to improve the redox balance and cardiac conditions.
HYPOTHESIS: Trapidil can improve the redox balance and contribute to functional improvements of the RV in PAH.
METHODS AND RESULTS: Male, 5week-old Wistar rats were divided into four groups: Control, Control + Trapidil, Monocrotaline and Monocrotaline + Trapidil. PAH was induced by an intraperitoneal injection of monocrotaline 60 mg/kg at day 0. Treatment started at day 7 (5 or 8 mg/kg/day) until day 14, when animals were euthanized after echocardiography and catheterism. Right ventricular systolic pressure and pressure/time derivatives were increased in monocrotaline animals. The increased right ventricular diameters in monocrotaline groups were reduced with trapidil. Monocrotaline groups showed higher lipid peroxidation and glutathione peroxidase activity. Trapidil reduced NADPH oxidases activities and increased the reduced glutathiones/total glutathiones ratio. Protein expression of phospholamban in RV was diminished in monocrotaline groups, whereas expression of RyR and SERCA was enhanced in the groups treated with trapidil.
CONCLUSION: Our data suggest that trapidil induces an improvement in RV remodeling in PAH model, mitigating the progression of the disease.
HYPOTHESIS: Trapidil can improve the redox balance and contribute to functional improvements of the RV in PAH.
METHODS AND RESULTS: Male, 5week-old Wistar rats were divided into four groups: Control, Control + Trapidil, Monocrotaline and Monocrotaline + Trapidil. PAH was induced by an intraperitoneal injection of monocrotaline 60 mg/kg at day 0. Treatment started at day 7 (5 or 8 mg/kg/day) until day 14, when animals were euthanized after echocardiography and catheterism. Right ventricular systolic pressure and pressure/time derivatives were increased in monocrotaline animals. The increased right ventricular diameters in monocrotaline groups were reduced with trapidil. Monocrotaline groups showed higher lipid peroxidation and glutathione peroxidase activity. Trapidil reduced NADPH oxidases activities and increased the reduced glutathiones/total glutathiones ratio. Protein expression of phospholamban in RV was diminished in monocrotaline groups, whereas expression of RyR and SERCA was enhanced in the groups treated with trapidil.
CONCLUSION: Our data suggest that trapidil induces an improvement in RV remodeling in PAH model, mitigating the progression of the disease.