scholarly journals Magnesium Sulfate Mitigates the Progression of Monocrotaline Pulmonary Hypertension in Rats

2019 ◽  
Vol 20 (18) ◽  
pp. 4622 ◽  
Author(s):  
Chao-Yuan Chang ◽  
Hung-Jen Shih ◽  
I-Tao Huang ◽  
Pei-Shan Tsai ◽  
Kung-Yen Chen ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Magnesium Sulfate ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Right Ventricular Hypertrophy ◽  
Male Rats ◽  
Wall Thickening ◽  
Artery Wall

We investigated whether magnesium sulfate (MgSO4) mitigated pulmonary hypertension progression in rats. Pulmonary hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). MgSO4 (100 mg/kg) was intraperitoneally administered daily for 3 weeks, from the seventh day after monocrotaline injection. Adult male rats were randomized into monocrotaline (MCT) or monocrotaline plus MgSO4 (MM) groups (n = 15 per group); control groups were maintained simultaneously. For analysis, surviving rats were euthanized on the 28th day after receiving monocrotaline. The survival rate was higher in the MM group than in the MCT group (100% versus 73.3%, p = 0.043). Levels of pulmonary artery wall thickening, α-smooth muscle actin upregulation, right ventricular systolic pressure increase, and right ventricular hypertrophy were lower in the MM group than in the MCT group (all p < 0.05). Levels of lipid peroxidation, mitochondrial injury, inflammasomes and cytokine upregulation, and apoptosis in the lungs and right ventricle were lower in the MM group than in the MCT group (all p < 0.05). Notably, the mitigation effects of MgSO4 on pulmonary artery wall thickening and right ventricular hypertrophy were counteracted by exogenous calcium chloride. In conclusion, MgSO4 mitigates pulmonary hypertension progression, possibly by antagonizing calcium.

56The SGLT2 inhibitor empagliflozin reduces mortality in experimental pulmonary hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B Chowdhury ◽  
V Z Luu ◽  
A Z Luu ◽  
M G Kabir ◽  
Y Pan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Sglt2 Inhibitor ◽  
Right Ventricular Hypertrophy ◽  
Male Rats ◽  
Vascular Remodelling ◽  
Prevention Study

Abstract Introduction Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion and profoundly reduces hospitalisation for heart failure and cardiovascular mortality in individuals with type 2 diabetes. While empagliflozin has been reported to reduce blood pressure, its effect on pulmonary arterial hypertension (PAH) is unknown. PAH is a serious and progressive disease that is characterised by pulmonary artery vasoconstriction, vascular remodelling, right ventricular hypertrophy, and ultimately heart failure. Purpose To investigate the impact of empagliflozin on PAH-associated mortality and the progression as well as reversal of PAH in monocrotaline (MCT)-treated Sprague-Dawley rats. Methods A total of 66 male rats (220–250 g) were randomly assigned to one of three studies. PAH was induced with a single intraperitoneal injection of MCT on day 0 and empagliflozin (10 mg/kg) was administered daily by oral gavage. Survival study: PAH was induced with 60 mg/kg MCT. Starting on day 1, rats were treated with empagliflozin (n=8) or vehicle (n=8) for 28 days and monitored for up to 45 days post-MCT injection. Prevention study: Rats were administered 60 mg/kg MCT and treated with empagliflozin (n=12) or vehicle (n=12) for 20 days from day 1 onwards. Reversal study: 21 days after being injected with 40 mg/kg MCT, rats were given empagliflozin (n=8) or vehicle (n=8) for 14 days. At the end of the treatment window, rats in the latter two studies underwent haemodynamic assessments before their tissues were harvested for histological review. Results Mortality rates between the two groups were significantly different (median survival 24 vs 33 days for vehicle vs empagliflozin; p<0.05). Compared to the MCT-vehicle-treated rats, the MCT-empagliflozin group had significantly lower mean pulmonary artery pressure (77.4±8.6 vs 51.0±4.9 mmHg [Prevention study]; 56.0±4.3 vs 43.0±3.4 mmHg [Reversal study]); higher pulmonary acceleration time (21.0±0.8 vs 27.4±1.4 ms [Prevention study] and 27.1±1.0 vs 33.4±1.3 ms [Reversal study]); and less right ventricular hypertrophy (0.52±0.01 vs 0.41±0.04 [Prevention study]). Histological assessments revealed significantly less medial wall thickening (50.8±2.2 vs 44.7±1.1 mm) and muscularisation (53.2±1.3 vs 43.6±2.1 mm) in pulmonary arterioles from the empagliflozin- vs vehicle-treated rats (p<0.001 for both). Conclusion This is the first study demonstrating that SGLT2 inhibition with empagliflozin lowers mortality in experimental pulmonary hypertension in part via reduced pulmonary vascular remodelling. Acknowledgement/Funding This study was supported by grants from the Canadian Institutes of Health Research.

scholarly journals The protective of baicalin on pulmonary hypertension vascular remodeling through regulation of TNF-α signaling pathway

2020 ◽  
Author(s):  
Xia Xue ◽  
Wen Jiang ◽  
Chao Sun ◽  
Jue Wang ◽  
Qian Xin ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Signaling Pathway ◽  
Vascular Remodeling ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Right Ventricular Hypertrophy ◽  
Intragastric Administration ◽  
Tnf Α

Abstract Background: Pulmonary hypertension (PH) is a life-threatening disease, so far no effective method for it. Baicalin can attenuate pulmonary artery pressure and reduce right ventricular hypertrophy in PH, however, the potential mechanism remains unexplored. Therefore, the main aim of the present study was to investigate the protective effect and of baicalin on experimental PH vascular remodeling, and reveal the underlying mechanism.Methods: Monocrotaline (MCT)-induced PH rats models was established, and baicalin was given by intragastric administration. Six weeks later, right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) were recorded, lung tissue hematoxylin-eosin (H&E) staining was analysis to reveal the effect of baicalin on MCT-induced PH. In Vitro, we established TNF-α induced pulmonary artery smooth muscle cells (PASMCs) to detect the inhibition of baicalin on vascular remodeling. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunofluorescence were used to detect the mRNA and protein expressions.Results: Our results indicated that baicalin could significantly attenuate MCT induced the RVSP and the right ventricular hypertrophy index (RVHI); inhibit pulmonary vascular remodeling and lung fibrosis. Moreover, our results showed baicalin could significantly decrease the expression of inflammatory cytokines, but increase the protein expression of bone morphogenetic protein type II receptor (BMPR2), ID1 and Smad1//5/8.Conclusion:Taken together, our present study confirmed the mechanism of baicalin against PH was associated with inhibition of TNF-α signaling pathway.

Cystamine Treatment Fails to Prevent the Development of Pulmonary Hypertension in Chronic Hypoxic Rats

2021 ◽  
pp. 1-15
Author(s):  
Lars K. Markvardsen ◽  
Lene D. Sønderskov ◽  
Christine Wandall-Frostholm ◽  
Estéfano Pinilla ◽  
Judit Prat-Duran ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Lung Tissue ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Right Ventricular Hypertrophy ◽  
Ventricular Systolic Pressure ◽  
Pulmonary Arterial ◽  
The Right

<b><i>Introduction:</i></b> Pulmonary hypertension is characterized by vasoconstriction and remodeling of pulmonary arteries, leading to right ventricular hypertrophy and failure. We have previously found upregulation of transglutaminase 2 (TG2) in the right ventricle of chronic hypoxic rats. The hypothesis of the present study was that treatment with the transglutaminase inhibitor, cystamine, would inhibit the development of pulmonary arterial remodeling, pulmonary hypertension, and right ventricular hypertrophy. <b><i>Methods:</i></b> Effect of cystamine on transamidase activity was investigated in tissue homogenates. Wistar rats were exposed to chronic hypoxia and treated with vehicle, cystamine (40 mg/kg/day in mini-osmotic pumps), sildenafil (25 mg/kg/day), or the combination for 2 weeks. <b><i>Results:</i></b> Cystamine concentration-dependently inhibited TG2 transamidase activity in liver and lung homogenates. In contrast to cystamine, sildenafil reduced right ventricular systolic pressure and hypertrophy and decreased pulmonary vascular resistance and muscularization in chronic hypoxic rats. Fibrosis in the lung tissue decreased in chronic hypoxic rats treated with cystamine. TG2 expression was similar in the right ventricle and lung tissue of drug and vehicle-treated hypoxic rats. <b><i>Discussion/Conclusions:</i></b> Cystamine inhibited TG2 transamidase activity, but cystamine failed to prevent pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial muscularization in the chronic hypoxic rat.

scholarly journals Stage IV Sarcoidosis with Cor pulmonale: A Case Report

2016 ◽  
Vol 30 (1) ◽  
pp. 37-42
Author(s):  
Mostashirul Haque ◽  
Tunaggina Afrin Khan ◽  
Md Rasul Amin ◽  
Montasin Rezwan ◽  
Md Rashidul Hasan ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Stage Iv ◽  
Pulmonary Involvement ◽  
Cor Pulmonale ◽  
Right Ventricular Hypertrophy ◽  
Pulmonary Artery Systolic Pressure ◽  
Strain Pattern

Sarcoidosis is a well known systemic disorder that invariably involves lungs. However, pulmonary hypertension and cor-pulmanle are not common due to pulmonary involvement of sarcoidosis. We report a case of pulmonary hypertension leading to corpulmonale due to sarcoidosis. An elderly female suffering from hypertension & sarcoidosis developed complications and arrived at the diagnosis by correlating various investigations. X-ray chest (P/A) showed cardiomegaly (right ventricular type), reticulo-nodular shadow involving both mid and lower zone; characteristic high resolution CT (HRCT) scan appearances include reticulonodular opacities; pulmonary function test showed restrictive type of defect; ECG showed right ventricular hypertrophy with strain pattern; in echocardiogram there were right ventricular hypertrophy (RVH) with pulmonary artery systolic pressure (PASP) of 63 mmHg indicating severe pulmonary arterial hypertension (PH); along with significantly elevated B-type natriuretic peptide(BNP) level.Bangladesh Heart Journal 2015; 30(1) : 37-42

scholarly journals Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways

2019 ◽  
Author(s):  
Rajamma Mathew ◽  
Jing Huang ◽  
Sanda Iacobas ◽  
Dumitru Iacobas
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Aerobic Glycolysis ◽  
Systolic Pressure ◽  
Smooth Muscle Contraction ◽  
Male Rats ◽  
Wall Thickening ◽  
High Morbidity ◽  
Antioxidant Genes ◽  
Ventricular Systolic Pressure

Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), lung histology and transcriptomes of six weeks old male rats with PH induced by: 1) hypoxia (HO), 2) administration of monocrotaline (CM) or 3) administration of monocrotaline and exposure to hypoxia (HM). The results in PH rats were compared to those in control rats (CO). After four weeks exposure, increased RVSP and RVH, pulmonary arterial wall thickening, and alteration of the lung transcriptome were observed in all PH groups. The HM group exhibited the largest alterations and also neointimal lesions and obliteration of lumen in small arteries. We found that the PH increased the expression of caveolin1, matrix metallopeptidase 2 and numerous inflammatory and cell proliferation genes. The cell-cycle, vascular smooth muscle contraction and the oxidative phosphorylation pathways, as well as their interplay were largely perturbed. Our results also suggest that the up-regulated Rhoa (ras homolog family member A) mediates its action through expression coordination with several ATPases. The upregulation of antioxidant genes and the extensive mitochondrial damage observed especially in HM group, indicate metabolic shift towards aerobic glycolysis.

Changes in pulmonary structure and function induced by monocrotaline intoxication

1981 ◽  
Vol 240 (2) ◽  
pp. H149-H155 ◽  
Author(s):  
F. Ghodsi ◽  
J. A. Will
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Pyrrolizidine Alkaloid ◽  
Histological Study ◽  
Right Ventricular Hypertrophy ◽  
Laboratory Animals ◽  
Functional Relationships ◽  
And Function

Monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, is known to be toxic to a variety of domestic and laboratory animals and to humans. Major pathological effects induced by monocrotaline poisoning include hepatic cirrhosis and megalocytosis, venocclusive disease, pulmonary hypertension, and right ventricular hypertrophy. The present investigation explored the structural and functional relationships that exist between pulmonary artery pressure, small pulmonary artery medial thickness, and right ventricular hypertrophy. The results of this physiological and histological study on monocrotaline-intoxicated rats has demonstrated that there is a positive correlation between progressive pulmonary hypertension, thickening of the medical wall of small pulmonary vessels, and right ventricular hypertrophy as a function of time.

Possible role of pulmonary blood volume in chronic hypoxic pulmonary hypertension

1993 ◽  
Vol 74 (6) ◽  
pp. 3020-3026 ◽  
Author(s):  
L. C. Ou ◽  
G. L. Sardella ◽  
N. S. Hill ◽  
C. D. Thron
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Blood Volume ◽  
Ventricular Hypertrophy ◽  
Chronic Hypoxia ◽  
Right Ventricular Hypertrophy ◽  
Hypoxic Pulmonary Hypertension ◽  
Pulmonary Blood Volume

Chronic hypoxia increases the total blood volume (TBV) and pulmonary arterial blood pressure (Ppa) and induces pulmonary vascular remodeling. The present study was undertaken to assess how the pulmonary blood volume (PBV) changes during hypoxia and the possible role of PBV in chronic hypoxic pulmonary hypertension. A novel method has been developed to measure the TBV, PBV, and Ppa in conscious rats. The method consists of chronic implantation of a loose ligature around the ascending aorta and pulmonary artery, so that when the ligature is drawn tightly, it traps the blood in the pulmonary vessels and left heart and simultaneously kills the rat. The pulmonary veins are then ligated to separate the left ventricular blood volume from the PBV. This surgical approach, together with chronic catheterization of the pulmonary artery and the use of 51Cr-labeled red blood cells, allows measurement of TBV, PBV, and Ppa. This method has been used to analyze the relationships between TBV and PBV and between Ppa or right ventricular hypertrophy and PBV in two rat strains with markedly different TBV and Ppa responses to chronic hypoxia. PBV per given lung weight did not increase and even decreased during hypoxia despite marked increases in TBV. There was a close correlation between Ppa or right ventricular hypertrophy and PBV in the two strains of chronically hypoxic animals, suggesting that a greater PBV plays a significant role in the development of severe chronic hypoxic pulmonary hypertension in the altitude-susceptible Hilltop rats.

scholarly journals Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 126 ◽  
Author(s):  
Rajamma Mathew ◽  
Jing Huang ◽  
Sanda Iacobas ◽  
Dumitru A. Iacobas
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Aerobic Glycolysis ◽  
Systolic Pressure ◽  
Smooth Muscle Contraction ◽  
Male Rats ◽  
Wall Thickening ◽  
High Morbidity ◽  
Antioxidant Genes ◽  
Ventricular Systolic Pressure

Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right-ventricular systolic pressure (RVSP), right-ventricular hypertrophy (RVH), lung histology, and transcriptomes of six-week-old male rats with PH induced by (1) hypoxia (HO), (2) administration of monocrotaline (CM), or (3) administration of monocrotaline and exposure to hypoxia (HM). The results in PH rats were compared to those in control rats (CO). After four weeks exposure, increased RVSP and RVH, pulmonary arterial wall thickening, and alteration of the lung transcriptome were observed in all PH groups. The HM group exhibited the largest alterations, as well as neointimal lesions and obliteration of the lumen in small arteries. We found that PH increased the expression of caveolin1, matrix metallopeptidase 2, and numerous inflammatory and cell proliferation genes. The cell cycle, vascular smooth muscle contraction, and oxidative phosphorylation pathways, as well as their interplay, were largely perturbed. Our results also suggest that the upregulated Rhoa (Ras homolog family member A) mediates its action through expression coordination with several ATPases. The upregulation of antioxidant genes and the extensive mitochondrial damage observed, especially in the HM group, indicate metabolic shift toward aerobic glycolysis.

scholarly journals Parathyroid hormone affects right heart hemodynamics and exacerbates pulmonary hypertension

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Y J Joki ◽  
H K Konishi ◽  
K T Takasu ◽  
T M Minamino
Keyword(s):  
Pulmonary Hypertension ◽  
Parathyroid Hormone ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Pulmonary Artery Pressure ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Right Heart ◽  
Pulmonary Hemodynamics ◽  
Artery Pressure

Abstract Background Pulmonary hypertension (PH) is characterized by increased pulmonary artery pressure and develops right heart failure. Parathyroid hormone (PTH) is secreted from parathyroid gland and regulates a calcium homeostasis. Recent studies have suggested that PTH also acts on the cardiovascular system and affects cardiovascular prognosis. We hypothesized that PTH would play a role in the pathogenesis of PH. Purpose This study aimed to investigate the effect of PTH on pulmonary hemodynamics. Method We measured serum PTH levels in patients who were suspected of PH and underwent right heart catheter examination. We used two types of PH animal models, hypoxia (Hx)-induced PH mouse model and Sugen/hypoxia (SuHx)-induced PH rat model. Hx mice were administered PTH daily for 3 weeks. SuHx rats underwent parathyroidectomy, after which they received SuHx treatment for 10weeks. We measured physical data and right ventricular systolic pressure (RVSP) in these models. We cultured pulmonary artery smooth muscle cell (PASMC) treated with PTH to analyze cell signaling, proliferation and migration. Result We enrolled 20 participants. PTH concentration was significantly correlated with mean pulmonary artery pressure (r=0.58, p=0.006) as well as with pulmonary vascular resistance (r=0.61, p=0.04). Receiver operating characteristic curve displayed a cut-off PTH level of 48.0pg/ml that offered optimal differentiation between patients with and without PH (100% sensitivity, 73% specificity). PTH treatment exacerbated right ventricular hypertrophy and increased RVSP (33.6mmHg vs. 48.2mmHg) in Hx mice compared with non-treated Hx mice (Figure 1). Conversely, parathyroidectomy significantly attenuated right ventricular hypertrophy and reduced RVSP (54.2mmHg vs. 29.3mmHg) in SuHx rats compared with sham-operated SuHx rats. PTH promoted migration and proliferation through ERK signaling in PASMC. Conclusion Our clinical and experimental data demonstrated a critical role of PTH in the development of PH and suggested that PTH would be a novel therapeutic target for PH treatment. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Young Scientists Figure 1. PTH treatment exacerbated RVSP

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