N-acylhydrazone derivative ameliorates monocrotaline-induced pulmonary hypertension through the modulation of adenosine AA2R activity

Alencar, Alexandre; Pereira, Sharlene L; Silva, Flavia E. da; Mendes, Luiza V.P.; Cunha, Valeria do Monti Nascimento; Lima, Lı́dia Moreira; Montagnoli, Tadeu L.; Caruso-Neves, Celso; Ferraz, Emanuelle B; Tesch, Roberta; Nascimento, José; Sant’Anna, Carlos Maurício R.; Fraga, Carlos A.M.; Barreiro, Eliezer J.; Sudo, Roberto T.; Zapata‐Sudo, Gisele

doi:10.1016/j.ijcard.2014.02.022

Cited by 32 publications

(63 citation statements)

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“…Rats in the MCT groups were given a single intraperitoneal (i.p.) injection of MCT at 60 mg/kg body weight to induce PH as published elsewhere (Alencar et al, 2014; Alencar et al, 2013; Zapata-Sudo et al, 2012). Rats in the control group were injected with the same volume of sterile saline.…”

Section: Methodsmentioning

confidence: 99%

“…Cardiac function was assessed by an echocardiographic system equipped with a 10-MHz mechanical transducer (Esaote model, CarisPlus, Florence, Italy), following the procedure previously described (Alencar et al, 2014; Lang et al, 2006). In order to confirm PH development induced by MCT, parameters were evaluated before, 14 days and 28 days after injection.…”

Section: Methodsmentioning

confidence: 99%

“…Animals performed a graded treadmill (EP–131, Insight, São Paulo, Brazil) run to exhaustion, in different times (before, 14 days after, and 28 days after MCT injection) in order to assess the exercise performance as published elsewhere (Alencar et al, 2014). At the endpoint of the protocol, rats were anesthetized with ketamine (80 mg/kg, i.p.)…”

Section: Methodsmentioning

confidence: 99%

“…The preparation of rat lung and RV subcellular fractions and the subsequent western blot analysis for sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a), phospholamban (PLB), tumor necrosis factor-alpha (TNF-α), endothelial nitric oxide synthase (eNOS), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH, used as loading control) proteins were performed as the already published work (Alencar et al, 2014). …”

Section: Methodsmentioning

confidence: 99%

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Activation of GPER ameliorates experimental pulmonary hypertension in male rats

Alencar

Montes

Montagnoli

et al. 2017

European Journal of Pharmaceutical Sciences

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Rationale Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling that leads to pulmonary congestion, uncompensated right-ventricle (RV) failure, and premature death. Preclinical studies have demonstrated that the G protein-coupled estrogen receptor (GPER) is cardioprotective in male rats and that its activation elicits vascular relaxation in rats of either sex. Objectives To study the effects of GPER on the cardiopulmonary system by the administration of its selective agonist G1 in male rats with monocrotaline (MCT)-induced PH. Methods Rats received a single intraperitoneal injection of MCT (60 mg/kg) for PH induction. Experimental groups were as follows: control, MCT + vehicle, and MCT + G1 (400 μg/kg/day subcutaneous). Animals (n = 5 per group) were treated with vehicle or G1 for 14 days after disease onset. Measurements and main results Activation of GPER attenuated exercise intolerance and reduced RV overload in PH rats. Rats with PH exhibited echocardiographic alterations, such as reduced pulmonary flow, RV hypertrophy, and left-ventricle dysfunction, by the end of protocol. G1 treatment reversed these PH-related abnormalities of cardiopulmonary function and structure, in part by promoting pulmonary endothelial nitric oxide synthesis, Ca2+ handling regulation and reduction of inflammation in cardiomyocytes, and a decrease of collagen deposition by acting in pulmonary and cardiac fibroblasts. Conclusions G1 was effective to reverse PH-induced RV dysfunction and exercise intolerance in male rats, a finding that have important implications for ongoing clinical evaluation of new cardioprotective and vasodilator drugs for the treatment of the disease.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Activation of GPER ameliorates experimental pulmonary hypertension in male rats

Alencar

Montes

Montagnoli

et al. 2017

European Journal of Pharmaceutical Sciences

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“…Progressive pulmonary vasculitis leads to increased vascular resistance and gradual arterial pressure increases beginning approximately one week after a single dose of MCT (Handoko et al 2008). MCT-induced PH in rats mimics several aspects of primary or secondary human PH, including endothelial cell dysfunction, vascular remodeling, and upregulation of inflammatory cytokines, and is therefore used as an appropriate in vivo PH model (Alencar et al 2014). Salvia Miltiorrhiza Bge.f.alba, a white flower variant of Salvia Miltiorrhiza Bge (Danshen), is different from genuine Danshen that has a purple corolla, and has been recognized as a new variety.…”

Section: Introductionmentioning

confidence: 99%

Salvia Miltiorrhiza Bge.f.alba Ameliorates the Progression of Monocrotaline-Induced Pulmonary Hypertension by Protecting Endothelial Injury in Rats

Wang

Cao

Cui

et al. 2015

Tohoku J. Exp. Med.

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Pulmonary hypertension (PH) is a life-threatening disease that is characterized by elevated pulmonary blood pressure, abnormally thickened pulmonary arteries, and right ventricular hypertrophy. Monocrotaline (MCT) has been used to generate an experimental model of PH in rats, with PH initiated from injuries of lung vascular endothelium. Salvia Miltiorrhiza Bge.f.alba is a widely used traditional herb in China, known to exert protective effects on vascular endothelial cell injury in animal experiments. However, the role of Salvia Miltiorrhiza Bge.f.alba in PH remains unclear. Thus, we investigated the effects of the aqueous extract of Salvia Miltiorrhiza Bge.f.alba (AESM) on MCT-induced PH and explored the pertinent mechanism. PH was induced in rats by a single subcutaneous injection of MCT (60 mg/kg body weight). Low or high dose (4.6 g/kg or 14 g/kg body weight) of AESM was then administered orally for 21 days to PH rats. Hemodynamic study showed that AESM reduced mean pulmonary artery pressure and improved right ventricle function. Lung pathological analysis revealed that AESM reduced wall thickness and lumen stenosis of pulmonary vessels. Also AESM ameliorated right ventricular hypertrophy. Measurement of biochemical parameters indicated that AESM decreased endothelin-1 and thromboxane A 2 in plasma and increased nitrogen monoxide and prostacyclin in the plasma and reduced the increase of transforming growth factor β 1 in lung tissue. Our results suggest that AESM may ameliorate the progression of MCT-induced PH in rats, at least in part by its protective effect on endothelial injury. Therefore, Salvia Miltiorrhiza Bge.f.alba could be useful in the treatment of PH.

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