scholarly journals Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

2020 ◽  
Vol 21 (19) ◽  
pp. 7077
Author(s):  
Olga Sadowska ◽  
Marta Baranowska-Kuczko ◽  
Anna Gromotowicz-Popławska ◽  
Michał Biernacki ◽  
Aleksandra Kicman ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricle ◽  
Plasminogen Activator ◽  
Leukocyte Count ◽  
Plasma Concentrations ◽  
Lung Edema ◽  
Human Pulmonary Artery ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

Cannabidiol (CBD) is known for its vasorelaxant (including in the human pulmonary artery), anti-proliferative and anti-inflammatory properties. The aim of our study was to examine the potential preventive effect of chronic CBD administration (10 mg/kg/day for three weeks) on monocrotaline (MCT)-induced pulmonary hypertension (PH) rats. PH was connected with elevation of right ventricular systolic pressure; right ventricle hypertrophy; lung edema; pulmonary artery remodeling; enhancement of the vasoconstrictor and decreasing vasodilatory responses; increases in plasma concentrations of tissue plasminogen activator, plasminogen activator inhibitor type 1 and leukocyte count; and a decrease in blood oxygen saturation. CBD improved all abovementioned changes induced by PH except right ventricle hypertrophy and lung edema. In addition, CBD increased lung levels of some endocannabinoids (anandamide, N-arachidonoyl glycine, linolenoyl ethanolamide, palmitoleoyl ethanolamide and eicosapentaenoyl ethanolamide but not 2-arachidonoylglycerol). CBD did not affect the cardiopulmonary system of control rats or other parameters of blood morphology in PH. Our data suggest that CBD ameliorates MCT-induced PH in rats by improving endothelial efficiency and function, normalization of hemostatic alterations and reduction of enhanced leukocyte count determined in PH. In conclusion, CBD may be a safe, promising therapeutic or adjuvant therapy agent for the treatment of human pulmonary artery hypertension.

Pulmonary hypertension is attenuated and ventilation-perfusion matching is maintained during chronic hypoxia in deer mice native to high altitude

2021 ◽  
Author(s):  
Claire M. West ◽  
Oliver H. Wearing ◽  
Rod G. Rhem ◽  
Graham R. Scott
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Right Ventricle ◽  
High Altitude ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Deer Mice ◽  
Maladaptive Response ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

Hypoxia at high altitude can constrain metabolism and performance, and can elicit physiological adjustments that are deleterious to health and fitness. Hypoxic pulmonary hypertension is a particularly serious and maladaptive response to chronic hypoxia, which results from vasoconstriction and pathological remodeling of pulmonary arteries, and can lead to pulmonary edema and right ventricle hypertrophy. We investigated whether deer mice (Peromyscus maniculatus) native to high altitude have attenuated this maladaptive response to chronic hypoxia, and whether evolved changes or hypoxia-induced plasticity in pulmonary vasculature might impact ventilation-perfusion (V-Q) matching in chronic hypoxia. Deer mouse populations from both high and low altitudes were born and raised to adulthood in captivity at sea level, and various aspects of lung function were measured before and after exposure to chronic hypoxia (12 kPa O2, simulating the O2 pressure at 4300 m) for 6-8 weeks. In lowlanders, chronic hypoxia increased right ventricle systolic pressure (RVSP) from 14 to 19 mmHg (P = 0.001), in association with thickening of smooth muscle in pulmonary arteries and right ventricle hypertrophy. Chronic hypoxia also impaired V-Q matching in lowlanders (measured at rest using SPECT-CT imaging), as reflected by increased log SD of the perfusion distribution (log SDQ) from 0.55 to 0.86 (P = 0.031). In highlanders, chronic hypoxia had attenuated effects on RVSP and no effects on smooth muscle thickness, right ventricle mass, or V-Q matching. Therefore, evolved changes in lung function help attenuate maladaptive plasticity and contribute to hypoxia tolerance in high-altitude deer mice.

scholarly journals Cyclosporin A Inhibits Hypoxia-induced Pulmonary Hypertension and Right Ventricle Hypertrophy

2006 ◽  
Vol 174 (6) ◽  
pp. 699-705 ◽  
Author(s):  
Nathalie Koulmann ◽  
Valérie Novel-Chaté ◽  
André Peinnequin ◽  
Rachel Chapot ◽  
Bernard Serrurier ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Cyclosporin A ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

scholarly journals Inhibition of Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 (MK2) is Protective in Pulmonary Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Mohammad Shafiq ◽  
Kumaravelu Jagavelu ◽  
Hina Iqbal ◽  
Pankaj Yadav ◽  
Debabrata Chanda ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Pulmonary Artery ◽  
Right Ventricle ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Pulmonary Artery Smooth Muscle ◽  
Human Pulmonary Artery

Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 (MK2), downstream to p38MAPK (p38mitogen-activated protein kinase), regulates cellular inflammation and proliferation. So far, the role of MK2 has been studied in many cardiovascular diseases, but it remains unexplored in pulmonary hypertension (PH). Therefore, to investigate the role of MK2 in the PH pathogenesis, human pulmonary artery smooth muscle cells were exposed to hypoxia (1% O 2 ) for 72 hours, and MK2 was inhibited by siRNA. We observed significantly increased MK2 expression, inflammatory cytokines, proliferation, mitochondrial dysfunction, and apoptosis resistance in hypoxic human pulmonary artery smooth muscle cells, which were reversed by treatment with MK2 siRNA. For in vivo studies, male Sprague Dawley rats were treated with monocrotaline (60 mg/kg, SC, once) to induce PH. To inhibit MK2, a peptide MMI-0100 (40 μg/kg, IP daily, 5 weeks for preventive and 3 weeks for curative study) was administered. MMI-0100 treatment decreased right ventricle pressure and hypertrophy, hallmarks of PH, in both preventive and curative study. MMI-0100-treated rats showed better cardiac functions as revealed by 2-dimensional echocardiography study. Furthermore, MMI-0100 reversed pulmonary vascular remodeling and improved pulmonary vascular relaxation in monocrotaline-treated rats. Finally, the above results were confirmed in MK2 knockout mice. MK2 knockout mice, received 600 mg/kg monocrotaline, subcutaneous weekly for 5 weeks, failed to develop PH and showed no increase in right ventricle pressure and hypertrophy. This study, therefore, proved that MK2 is involved in PH, and its inhibition may be a novel target for PH treatment.

scholarly journals Inhibition of BET Proteins Reduces Right Ventricle Hypertrophy and Pulmonary Hypertension Resulting from Combined Hypoxia and Pulmonary Inflammation

2018 ◽  
Vol 19 (8) ◽  
pp. 2224 ◽  
Author(s):  
Clovis Chabert ◽  
Saadi Khochbin ◽  
Sophie Rousseaux ◽  
Sylvie Veyrenc ◽  
Rebecca Furze ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Chronic Hypoxia ◽  
Pulmonary Inflammation ◽  
Male Rats ◽  
Hemodynamic Parameters ◽  
Terminal Domain ◽  
Co Morbidity ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

Pulmonary hypertension is a co-morbidity, which strongly participates in morbi-mortality in patients with chronic obstructive pulmonary disease (COPD). Recent findings showed that bromodomain-containing proteins, in charge of reading histone acetylation, could be involved in pulmonary arterial hypertension. Our aim was to study the effect of I-BET151, an inhibitor of bromodomain and extra-terminal domain (BET), on the right ventricle hypertrophy and pulmonary hypertension, induced by a combination of chronic hypoxia and pulmonary inflammation, as the two main stimuli encountered in COPD. Adult Wistar male rats, exposed to chronic hypoxia plus pulmonary inflammation (CHPI), showed a significant right ventricle hypertrophy (+57%, p < 0.001), an increase in systolic pressure (+46%, p < 0.001) and in contraction speed (+36%, p < 0.001), when compared to control animals. I-BET151 treated animals (CHPI-iB) showed restored hemodynamic parameters to levels similar to control animals, despite chronic hypoxia plus exposure to pulmonary inflammation. They displayed lower right ventricle hypertrophy and hematocrit compared to the CHPI group (respectively −16%, p < 0.001; and −9%, p < 0.05). Our descriptive study shows a valuable effect of the inhibition of bromodomain and extra-terminal domain proteins on hemodynamic parameters, despite the presence of chronic hypoxia and pulmonary inflammation. This suggests that such inhibition could be of potential interest for COPD patients with pulmonary hypertension. Further studies are needed to unravel the underlying mechanisms involved and the net benefits of inhibiting adaptations to chronic hypoxia.

Supplementation of Creatine and Ribose Prevents Apoptosis and Right Ventricle Hypertrophy in Hypoxic Hearts

2013 ◽  
Vol 19 (39) ◽  
pp. 6873-6879 ◽  
Author(s):  
Anna Caretti ◽  
Paola Bianciardi ◽  
Marina Marini ◽  
Provvidenza Abruzzo ◽  
Alessandra Bolotta ◽  
...  
Keyword(s):  
Right Ventricle ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

scholarly journals TETRALOGI FALLOT DAN ATRESIA PULMONAL

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Alice I. Supit ◽  
Erling D. Kaunang
Keyword(s):  
Patent Ductus Arteriosus ◽  
Right Ventricle ◽  
Tetralogy Of Fallot ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Ductus Arteriosus ◽  
Ventricle Hypertrophy ◽  
The Right ◽  
Right Ventricle Hypertrophy ◽  
Patent Ductus

Abstract: Congenital heart disease is a structural defect due to the malformation of the heart, aorta, and or great blood vessels. It is the most frequent congenital malformation in newborn babies. Tetralogy of Fallot is one of the congenital heart diseases (CHD) with central cyanosis, and covers 5-10% of all CHD. We reported a boy of one year old with Tetralogy of Fallot and pulmonal atresia (ToF-PA), associated with bronchopneumonia. The diagnosis was based on anamnesis, physical examination, and other supporting examinations. The chest X-ray showed a normal sized heart (CTR 57%) with coer-en-sabot shape, and right and left parahilar infiltration, which resulted in bronchopneumonia and ToF. The electrocardiography showed a right deviation of axis and a hypertrophy of the right ventricle; the echocardiography showed a right ventricle hypertrophy, an over-riding aorta, a large malalignment of the ventricular septal defect, no visualization of pulmonar artery, and no visualization of patent ductus arteriosus (PDA). Conclusion: Based on all the tests performed, the diagnosis of this patient was Tetralogy of Fallot and pulmonal atresia (ToF-PA), associated with bronchopneumonia. The prognosis related to bronchopneumonia in this case was good due to the use of antibiotics. Keywords: tetralogy of Fallot, pulmona atresia, bronchopneumonia.  Abstrak: Penyakit jantung bawaan (PJB) ialah kelainan struktural akibat malformasi jantung, aorta dan atau pembuluh darah besar, dan merupakan kelainan kongenital tersering pada bayi baru lahir. Tetralogi Fallot merupakan salah satu PJB dengan sianosis sentral, dan mencakup 5-10% dari seluruh PJB. Kami melaporkan kasus seorang anak laki-laki berusia satu tahun dengan Tetralogi Fallot dan atresia pulmonal (ToF-PA) disertai bronkopneumonia. Diagnosis ditegakkan melalui anamnesis, pemeriksaan fisik, dan pemeriksaan penunjang. Hasil ekspertisi foto toraks AP memperlihatkan ukuran jantung normal (CTR 57%) berbentuk coer-en-sabot, dan pada paru-paru terlihat infiltrat parahilar kanan dan kiri serta corakan vaskular paru berkurang yang menunjukkan suspek bronkopneumonia dan ToF. Elektrokardiografi memperlihatkan deviasi aksis ke kanan dan hipertrofi ventrikel kanan, dan pada ekokardiografi tampak right ventricle hypertrophy, overriding aorta, VSD malalignment besar, tidak tampak visualisasi arteri pulmonal, dan tidak tampak patent ductus arteriosus (PDA) dengan hasil Tetralogi Fallot dan atresia pulmonal. Simpulan: Berdasarkan hasil pemeriksaan yang dilakukan, diagnosis pasien ini ialah Tetralogi Fallot dan atresia pulmonal (ToF-PA) disertai bronkopneumonia. Prognosis bronkopenumonia pada kasus ini baik yang dapat diatasi dengan antibiotika.Kata kunci: tetralogi Fallot, atresia pulmonal, bronkopneumonia.  

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