Trapidil improves hemodynamic, echocardiographic and redox state parameters of right ventricle in monocrotaline-induced pulmonary arterial hypertension model.

Autor: Türck P; Department of Physiology, Basic Sciences Institute of Health, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., Lacerda DS; Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Basic Sciences Institute of Health, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., Carraro CC; Department of Physiology, Basic Sciences Institute of Health, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., de Lima-Seolin BG; Department of Physiology, Basic Sciences Institute of Health, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., Teixeira RB; Department of Physiology, Basic Sciences Institute of Health, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., Poletto Bonetto JH; Department of Physiology, Basic Sciences Institute of Health, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., Colombo R; Laboratory of Pharmacology and Physiology, Universidade de Caxias do Sul (UCS), Rio Grande do Sul, Brazil., Schenkel PC; Department of Physiology, Basic Sciences Institute of Health, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., Belló-Klein A; Department of Physiology, Basic Sciences Institute of Health, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., da Rosa Araujo AS; Department of Physiology, Basic Sciences Institute of Health, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil; Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Basic Sciences Institute of Health, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil. Electronic address: alex.rosa@ufrgs.br.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2018 Jul; Vol. 103, pp. 182-190. Date of Electronic Publication: 2018 Apr 24.
DOI: 10.1016/j.biopha.2018.04.001
Abstrakt: 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.
(Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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