Hypoxia increases pulmonary arterial thromboxane receptor internalization independent of receptor sensitization

Publication date: Available online 12 October 2014 Source:Pulmonary Pharmacology & Therapeutics Author(s): J. Fediuk , A.S. Sikarwar , P.P. Lizotte , M. Hinton , N. Nolette , S. Dakshinamurti Persistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by sustained vasospasm and an increased thromboxane:prostacyclin ratio. Thromboxane (TP) receptors signal via Gαq to mobilize IP3 and Ca2+, causing pulmonary arterial constriction. We have previously reported increased TP internalization in hypoxic pulmonary arterial (PA) myocytes. Serum-deprived PA myocytes were grown in normoxia (NM) or hypoxia (HM) for 72 h. TP localization was visualized in agonist-naïve and -challenged NM and HM by immunocytochemistry. Pathways for agonist-induced TP receptor internalization were determined by inhibiting caveolin- or clathrin-mediated endocytosis, and caveolar fractionation. Roles of actin and tubulin in TP receptor internalization were assessed using inhibitors of tubulin, actin-stabilizing or -destabilizing agents. PKA, PKC or GRK activation and inhibition were used to determine the kinase responsible for post-agonist receptor internalization. Agonist-naïve HM had decreased cell surface TP, and greater TP internalization after agonist challenge. TP protein did not sort with caveolin-rich fractions. Inhibition of clathrin prevented TP internalization. Both actin-stabilizing and -destabilizing agents prevented TP endocytosis in NM, while normalizing T...
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research

Related Links:

Bone Marrow Transplantation, Published online: 12 December 2019; doi:10.1038/s41409-019-0769-9Diagnosis of pulmonary hypertension by noninvasive methods in hematopoietic cell transplant patients with myelofibrosis
Source: Bone Marrow Transplantation - Category: Hematology Authors: Source Type: research
Kv11.1 potassium channels are essential for heart repolarization. Prescription medication that blocks Kv11.1 channels lengthens the ventricular action potential and causes cardiac arrhythmias. Surprisingly little is known about the Kv11.1 channel expression and function in the lung tissue. Here we report that Kv11.1 channels were abundantly expressed in the large pulmonary arteries (PAs) of healthy lung tissues from humans and rats. Kv11.1 channel expression was increased in the lungs of humans affected by chronic obstructive pulmonary disease –associated pulmonary hypertension and in the lungs of rats with pulmonary...
Source: American Journal of Pathology - Category: Pathology Authors: Tags: Regular article Source Type: research
We thank Wang et al. for their comments and for bringing forward the challenges in managing care of patients with pulmonary hypertension (PH) and stroke. We acknowledge multiple possible mechanisms of stroke in patients with PH, and we highlighted them in our work, including paradoxical emboli and atrial fibrillation [1]. However, polycythemia (increased red cells) or other myeloproliferative disorders are considered to be a cause and not a consequence of PH [2,3]. In mice models, Sala et al. have showed that chronic hypoxia could lead to both PH and polycythemia [4].
Source: International Journal of Cardiology - Category: Cardiology Authors: Tags: Letter to the Editor Source Type: research
Most published studies addressing the role of hypoxia inducible factors (HIFs) in hypoxia-induced pulmonary hypertension development employ models that may not recapitulate the clinical setting, including the use of animals with pre-existing lung/vascular defects secondary to embryonic HIF ablation or activation. Furthermore, critical questions including how and when HIF signalling contributes to hypoxia-induced pulmonary hypertension remain unanswered. Normal adult rodents in which global HIF1 or HIF2 was inhibited by inducible gene deletion or pharmacological inhibition (antisense oligonucleotides (ASO) and small molecul...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Pulmonary vascular disease Original Articles: Pulmonary vascular disease Source Type: research
Pulmonary hypertension (PH) is a diverse collection of vascular disorders that cause remodelling of small pulmonary arteries, resulting in increases in pulmonary vascular resistance and pulmonary arterial pressure. The World Health Organization classifies these disorders into five groups. Group III includes pulmonary hypertension associated with hypoxic lung disorders such as COPD. While not everyone with COPD develops pulmonary hypertension, those who do are more likely to experience acute exacerbations, hospitalisations, and poorer outcomes. Because alveolar hypoxia is a key element driving this response, investigators h...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Editorials Source Type: research
Chronic thromboembolic pulmonary hypertension (CTEPH) is classified within group 4 pulmonary hypertension (PH), and is characterized by organized thrombi, which causes elevation of pulmonary artery and vascular remodeling leading to further deterioration of PH. The recent therapeutic options for CTEPH consist of following 3 major treatment, surgical treatment, interventional treatment, and medical treatment.
Source: International Journal of Cardiology - Category: Cardiology Authors: Tags: Editorial Source Type: research
Condition:   Hypertension, Pulmonary Interventions:   Other: Blood Sample;   Device: ReCIVA® Breath Sampler and CASPER air supply unit Sponsor:   Janssen Research & Development, LLC Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Publication date: Available online 10 December 2019Source: European Journal of RadiologyAuthor(s): Arun Jose, Akhil Kher, Robert E. O’Donnell, Jean M. ElwingAbstractPurposeTargeted treatment for pulmonary arterial hypertension (PAH), diagnosed via right heart catheterization (RHC), has been shown to improve morbidity and mortality. Identifying characteristics that predict clinical worsening has been challenging. We sought to evaluate the role of cardiac Magnetic Resonance Imaging (CMR) as a predictor of clinical worsening in a cohort of treatment-naïve pulmonary hypertension (PH) patients.MethodsWe performed a r...
Source: European Journal of Radiology - Category: Radiology Source Type: research
Right ventricular (RV) failure, a determinant of outcomes in pulmonary hypertension (PH), occurs when the right ventricle cannot compensate for increased afterload. The authors showed that RV stroke work (RVSW) can be estimated in children with PH as the product of stroke volume and RV pressure and is related to adverse outcomes. The aim of this study was to test the hypothesis that ventricular-vascular (VV) mismatch (high afterload and low RVSW) is associated with echocardiographic measures of RV performance and adverse outcomes.
Source: Journal of the American Society of Echocardiography - Category: Cardiology Authors: Source Type: research
Premature neonates 30 –55 mm Hg promotes pulmonary vasodilation. Targeting saturations of 80–85% by 5 min, 85–95% by 10 min during resuscitation and 90–95% during the postnatal course are appropriate targets for routine management of preterm infants.
Source: Seminars in Fetal and Neonatal Medicine - Category: Perinatology & Neonatology Authors: Source Type: research
More News: Drugs & Pharmacology | Hypertension | Pulmonary Hypertension | Respiratory Medicine