Low Thyroid Hormones Level Attenuates Mitochondrial Dysfunction and Right Ventricular Failure in Pulmonary Hypertensive Rats.

This study is to investigate the repercussions of hypothyroidism in the pathophysiological progression of pulmonary arterial hypertension (PAH). While the control (CTL, n = 5) male Wistar rats received vehicle, PAH was induced with monocrotaline (MCT group, n = 15). Hypothyroidism was induced in a subset of rats by methimazole 3 weeks prior to the MCT injection (MMZ + MCT group, n = 15). Plasma thyroid hormones were measured by radioimmunoassay. Electrocardiographic, echocardiographic, and hemodynamic analyses were performed to evaluate the progression of PAH. Gene expression of antioxidant enzymes and cardiac hypertrophy markers were assessed by qPCR. Mitochondrial respiration, ATP levels, and ROS production were measured in right ventricular (RV) samples. Plasma T3 and T4 decreased in both MCT and MMZ + MCT groups (p < 0.05). Right ventricular systolic pressure (RVSP) increased, and RV - dP/dt, + dP/dt, and contractility index decreased in the MCT versus the CTL group and remained within control levels in the MMZ + MCT group (p < 0.05). Relative RV weight, RV wall thickness, RV diastolic area, and relative lung weight were augmented in the MCT versus the CTL group, whereas all parameters were improved to the CTL levels in the MMZ + MCT group (p < 0.05). Only the MCT group exhibited an increased duration of QTc interval compared to the baseline period (p < 0.05). ADP-induced mitochondrial respiration and ATP levels were decreased, and ROS production was increased in MCT versus the CTL group (p < 0.05), while the MMZ + MCT group exhibited increased mitochondrial respiration versus the MCT group (p < 0.05). Hypothyroidism attenuated the RV mitochondrial dysfunction and the pathophysiological progression of MCT-induced PAH.

Souza NSC ，Barenco-Marins T ，Ferraz AP ，Barbosa RAQ ，Maciel L ，Ponte CG ，Seara FAC ，Olivares EL ，Nascimento JHM ... -  《-》

Effect of free and nanoemulsified β-caryophyllene on monocrotaline-induced pulmonary arterial hypertension.

Carraro CC ，Turck P ，Bahr A ，Donatti L ，Corssac G ，Lacerda D ，da Rosa Araujo AS ，de Castro AL ，Koester L ，Belló-Klein A ... -  《-》

Sulforaphane Improves Redox Homeostasis and Right Ventricular Contractility in a Model of Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance (PVR), imposing overload on the right ventricle (RV) and imbalance of the redox state. Our study investigated the influence of treatment with sulforaphane (SFN), found in cruciferous vegetables, on RV remodeling and redox homeostasis in monocrotaline (MCT)-induced PAH. Male Wistar rats were separated into 4 groups: control (CTR); CTR + SFN; MCT; and MCT + SFN. PAH induction was implemented by a single dose of MCT (60 mg/kg intraperitoneally). Treatment with SFN (2.5 mg/kg/day intraperitoneally) started on the seventh day after the MCT injection and persisted for 2 weeks. After 21 days of PAH induction, echocardiographic, hemodynamic, and oxidative stress evaluation was performed. The MCT group showed an increase in RV hypertrophy, RV systolic area, RV systolic, mean pulmonary artery pressure, and PVR and exhibited a decrease in the RV outflow tract acceleration time/ejection time ratio, RV fractional shortening, and tricuspid annular plane systolic excursion compared to CTR ( P < 0.05). SFN-treated PAH attenuated detrimental changes in tricuspid annular plane systolic excursion, mean pulmonary artery pressure, and PVR parameters. Catalase levels and the glutathione/Glutathione disulfide (GSSG) ratio were diminished in the MCT group compared to CTR ( P < 0.05). SFN increased catalase levels and normalized the glutathione/GSSG ratio to control levels ( P < 0.05). Data express the benefit of SFN treatment on the cardiac function of rats with PAH associated with the cellular redox state.

Conzatti A ，Colombo R ，Siqueira R ，Campos-Carraro C ，Turck P ，Luz de Castro A ，Belló-Klein A ，Sander da Rosa Araujo A ... -  《-》

Increased in vivo mitochondrial oxygenation with right ventricular failure induced by pulmonary arterial hypertension: mitochondrial inhibition as driver of cardiac failure?

Balestra GM ，Mik EG ，Eerbeek O ，Specht PA ，van der Laarse WJ ，Zuurbier CJ ... -  《RESPIRATORY RESEARCH》

Effect of estrogen on right ventricular remodeling of monocrotaline-induced pulmonary arterial hypertension in rats and its mechanism.

Liu Z ，Duan YL ，Ge SL ，Zhang CX ，Gong WH ，Xu JJ ... -  《-》