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

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AbstractPurpose of reviewPulmonary hypertension (PH) is a complex, progressive abnormal physiologic and hemodynamic state seen in many conditions. The purpose of this review is to discuss the updated clinical and hemodynamic classification systems and diagnostic criteria of PH, discuss the role of noninvasive imaging for diagnosing PH, and outline a diagnostic pathway to facilitate targeted therapies.Recent findingsPH is defined as a mean pulmonary arterial pressure (mPAP)>  20 mmHg since the sixth World Symposium on Pulmonary Hypertension (WSPH) in 2018, a lower threshold than the longstanding definition of...
Source: Current Treatment Options in Cardiovascular Medicine - Category: Cardiology Source Type: research
In this study, we investigated the effects of the ACE2 activator diminazene aceturate (DIZE) on the development of PH secondary to left ventricular dysfunction. A model of PH secondary to left ventricular dysfunction was established in 6-week-old Wistar rats by ascending aortic banding for 42 days. The hemodynamics and pulmonary expression of ACE, Ang II, ACE2, Ang-(1-7), and the Ang-(1-7) MAS receptor were investigated in the early treatment group, which was administered DIZE (15 mg/kg/day) from days 1 to 42, and in the late treatment group, administered DIZE (15 mg/kg/day) from days 29 to 42. Sham-operated rats served as...
Source: International Journal of Medical Sciences - Category: Biomedical Science Tags: Int J Med Sci Source Type: research
PMID: 33031025 [PubMed - as supplied by publisher]
Source: Circulation Research - Category: Cardiology Authors: Tags: Circ Res Source Type: research
Abstract BACKGROUND: Pulmonary vascular resistance (PVR) and compliance are comparable in proximal and distal chronic thromboembolic pulmonary hypertension (CTEPH). However, proximal CTEPH is associated with inferior right ventricular (RV) adaptation. Early wave reflection in proximal CTEPH may be responsible for altered RV function. The aims of the study are 1) investigate whether reflected pressure returns sooner in proximal than in distal CTEPH, and 2) elucidate whether timing of reflected pressure is related to RV dimensions, ejection fraction (RVEF), hypertrophy and wall stress. METHODS: Right heart cath...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research
New Brunswick, N.J., October 8, 2020 – Johnson &Johnson (NYSE: JNJ) (the Company) today announced the European Commission (EC), acting on behalf of the European Union (EU) Member States, has approved an Advance Purchase Agreement in which the Janssen Pharmaceutical Companies will supply 200 million doses of its COVID-19 vaccine candidate to EU Member States following approval or authorization from regulators. The EU Member States also have the option to secure up to 200 million additional doses.“The COVID-19 pandemic continues to threaten communities worldwide and we have a responsibility to ensure access t...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Our Company Source Type: news
The objective of this study is to report the outcomes after Shone's complex repair, the growth of mitral and aortic valve and LVOT, and long ‐term survival.MethodsThis retrospective study included all patients diagnosed with Shone's complex, who underwent biventricular repair. Data including patients' characteristics, type of the MV lesion and the associated lesions were collected. Patients were followed up regularly with echocardiography, and the changes in mitral and aortic valvez‐score and LVOTz‐score were recorded.ResultsThirty ‐seven patients were included in the study, the median age was 3.4 months, and 11 pa...
Source: Journal of Cardiac Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: ORIGINAL ARTICLE Source Type: research
AbstractObjectiveTo evaluate the effect of low dose vasopressin on the hemodynamics of neonates with persistent pulmonary hypertension and catecholamine refractory shock.MethodsThis retrospective study was conducted in a level III NICU of a tertiary care teaching hospital, south India. Eighteen neonates with hypoxemic respiratory failure due to persistent pulmonary hypertension of newborn with catecholamine refractory shock were studied. Neonates were managed for hypotension with conventional inotropic support with the additional use of low dose vasopressin (LDV). Effect of vasopressin on oxygenation index (OI), blood pres...
Source: Indian Journal of Pediatrics - Category: Pediatrics Source Type: research
Authors: Tian Z, Jiang X, Jing ZC Abstract INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by the presence of organized thromboembolic material and proliferative fibrous intima occluding varying degrees of the pulmonary arteries, and is also accompanied by small vessel vasculopathy in occluded and non-occluded pulmonary vasculature. The similarity in hemodynamics and pathophysiology between CTEPH and group 1 pulmonary arterial hypertension provides the rationale for clinical use of pulmonary arterial hypertension (PAH)-specific therapy. AREAS COVERED: The authors present the...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
To investigate the effects of mandible advanced device (MAD) therapy for obstructive sleep apnea-hypopnea syndrome (OSAHS) on nitric oxide (NO) release and changes in pulmonary artery pressure and structure.
Source: Journal of Oral and Maxillofacial Surgery - Category: ENT & OMF Authors: Source Type: research
Publication date: Available online 5 October 2020Source: Journal of the Formosan Medical AssociationAuthor(s): Zheng-Wei Chen, Cho-Kai Wu, Ping-Hung Kuo, Hsao-Hsun Hsu, Cheng-Hsuan Tsai, Chien-Ting Pan, Juey-Jen Hwang, Chi-Lun Ko, Yu-Sen Huang, Takeshi Ogo, Yen-Hung Lin
Source: Journal of the Formosan Medical Association - Category: General Medicine Source Type: research
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