Adel Zrein, Amina M Bagher, Alexander P Young, Eileen M Denovan-Wright, Melanie E M Kelly
The endothelin receptor A (ETA) and endothelin receptor B (ETB) are G protein-coupled receptors that are co-expressed in vascular smooth muscle cells. Endothelin-1 (ET-1) activates endothelin receptors to cause microvascular vasoconstriction. Previous studies have shown that heteromerization between ETA and ETB prolongs Ca2+ transients, leading to prolongation of Gαq -dependent signaling and sustained vasoconstriction. We hypothesized that these effects are in part mediated by the resistance of ETA/ETB heteromers to β-arrestin recruitment and subsequent desensitization...
August 3, 2020: Canadian Journal of Physiology and Pharmacology
Jinchao Zhang, Jing Hu, Xiujuan He, Yujiao Meng, Guangkun Chen, Zhaoxia Chen, Jingjing Lü, Ping Li
OBJECTIVE: To evaluate the effectiveness of Chinese herbal medicine for primary Raynaud's phenomenon (PRP). METHODS: The Cochrane Central Register of Controlled Trials, PubMed, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database were searched up to February 13, 2018. Randomized controlled trials (RCTs) on treatment of PRP with Chinese herbal medicine compared with placebo, blank control, lifestyle changes, or calcium antagonists were identified and reviewed...
August 2020: Journal of Traditional Chinese Medicine
Yan Liu, Su Liang, Peili Bu, Ershun Liang, Fangfang Yan, Yifan Xing, Pengfei Zhang
The aim of the present study was to validate the beneficial role of Radix Puerariae in rebalancing the plasma levels of endothelin, angiotensin II (AngII) and calcitonin gene-related peptide (CGRP) in patients with essential hypertension (EHT). A total of 150 patients with EHT were enrolled consecutively and randomized to receive antihypertensive drugs according to guideline-directed medical therapy (GDMT group) and GDMT plus Radix Puerariae (GDMT + RP group). The blood pressure was recorded biweekly. At baseline and at the end of the follow-up (12 weeks), the plasma levels of endothelin, AngII and CGRP were detected, whilst the left ventricular (LV) diastolic function was evaluated by echocardiography...
August 2020: Experimental and Therapeutic Medicine
Sergery Gurevich, Kurt W Prins
Pulmonary hypertension (PH) is a heterogeneous group of diseases defined by a mean pulmonary arterial pressure greater than 20 mmHg. Clinically, PH is classified into five groups and the group of PH generally defines the cause of PH and the therapeutic options. Currently, medical therapies that target the prostacyclin, endothelin, and nitric oxide pathways are used in pulmonary arterial hypertension and chronic thromboembolic PH (CTEPH) patients. Moreover, surgery can improve outcomes in PH as pulmonary thromboendarterectomy can be curative for CTEPH and lung transplantation is used for end-stage PH...
August 1, 2020: Catheterization and Cardiovascular Interventions
Lyudmyla V Dubyk, Oleksandr M Yuzko, Nataliia V Chernetska, Tetiana R Kolotylo
OBJECTIVE: The aim is to analyze the value of endothelial dysfunction markers during pregnancy. PATIENTS AND METHODS: Materials and methods: We have examined 153 pregnant women to identify endothelial dysfunction markers of endothelin-1, nitrogen oxide (NO) that have been studiedusing immunoenzymometric sets for an uncomplicated and complicated pregnancy. RESULTS: Results: We found that the concentration of endothelin-1 repeatedly exceeded the rates in pregnant women with miscarriages than during physiological pregnancy...
2020: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Tetiana B Oleshko, Iryna S Chaika, Tetiana M Oleshko, Viktoriia Yu Harbuzova
OBJECTIVE: The aim: Investigate the effect of Lys198Asn polymorphism of the EDN1 gene on ischemic atherothrombotic stroke characteristics. PATIENTS AND METHODS: Materials and methods: Venous blood of 170 patients with ischemic atherothrombotic stroke (IAS) and 124 patients without cerebrovascular pathology, who made up the control group, used for the study. Lys198Asn (rs5370) polymorphism of the EDN1 gene was determined by the polymerase chain reaction method followed by restriction fragment length analysis...
2020: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Hossein-Ardeschir Ghofrani, Ekkehard Grünig, Pavel Jansa, David Langleben, Stephan Rosenkranz, Ioana R Preston, Franck Rahaghi, Namita Sood, Dennis Busse, Christian Meier, Marc Humbert
Many patients with pulmonary arterial hypertension do not achieve treatment goals with monotherapy, and therefore combination therapy is becoming the standard of care. The soluble guanylate cyclase stimulator riociguat is licensed for the treatment of pulmonary arterial hypertension; here we present findings from patients who were receiving combined riociguat plus endothelin receptor antagonists or non-intravenous prostanoids in the randomized, placebo-controlled PATENT-1 study and its open-label extension (PATENT-2)...
July 2020: Pulmonary Circulation
Amaresh K Ranjan, Seema Briyal, Anil Gulati
The development of effective drugs for stroke is urgently required as it is the 2nd largest killer in the world and its incidence is likely to increase in the future. We have demonstrated cerebral endothelin B receptors (ETBR) as a potential target to treat acute cerebral ischemic stroke. However, the mechanism of ETBR mediated neural regeneration and repair remains elusive. In this study, a permanent middle cerebral artery occluded (MCAO) rat model was used. Sovateltide (an ETBR agonist) injected intravenously showed better survival and neurological and motor function improvement than control...
July 29, 2020: Scientific Reports
Hisataka Maki, Toru Hara, Masaki Tsuji, Akihito Saito, Shun Minatsuki, Toshiro Inaba, Eisuke Amiya, Yumiko Hosoya, Masaru Hatano, Hiroyuki Morita, Atsushi Yao, Koichiro Kinugawa, Issei Komuro
Therapeutic strategies for pulmonary arterial hypertension (PAH) have made remarkable progress over the last two decades. Currently, 3 types of drugs can be used to treat PAH; prostacyclins, phosphodiesterase 5 inhibitors, and endothelin receptor antagonists (ERA). In Japan, the first generation ERA bosentan was reimbursed in 2005, following which the 2nd generation ERAs ambrisentan and macitentan were reimbursed in 2009 and 2015, respectively. The efficacy of each ERA on hemodynamics in PAH patients remains to be elucidated...
2020: International Heart Journal
Irina A Mandel, Yuri K Podoksenov, Irina V Suhodolo, Darya A An, Sergey L Mikheev, Andrey Yu Podoksenov, Yulia S Svirko, Anna M Gusakova, Vladimir M Shipulin, Andrey G Yavorovskiy
The aim of the experiment was to evaluate the effect of preconditioning based on changes in inspiratory oxygen fraction on endothelial function in the model of ischemia-reperfusion injury of the myocardium in the condition of cardiopulmonary bypass. The prospective randomized study included 32 rabbits divided into four groups: hypoxic preconditioning, hyperoxic preconditioning, hypoxic-hyperoxic preconditioning, and control group. All animals were anesthetized and mechanically ventilated. We provided preconditioning, then started cardiopulmonary bypass, followed by induced acute myocardial infarction (ischemia 45 min, reperfusion 120 min)...
July 27, 2020: International Journal of Molecular Sciences
Mohammadreza Talebnejad, Peyman Khazaei, Hamidreza Jahanbani-Ardakani, Ebrahim Moghimi-Sarani, Zahra Mohammadreza Khalili
BACKGROUND: Methamphetamine (Meth) is a highly addictive and hallucinogenic agent which is used as the second most common illicit drug globally. Meth could affect the retina and optic nerve by inducing the release of vasoconstrictive agents such as endothelin 1 and induction of severe oxidative stress with accumulation of reactive oxygen species. AIM: To evaluate the effects of chronic Meth abuse on the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) and the Bruch's membrane opening minimum rim width (MRW)...
July 26, 2020: Neurotoxicology
H Kazimoglu, E Uysal, M Dokur, A O Gurer, K Batcioglu, B A Uyumlu, E Petekkaya, M Karadag
AIM: This study aims to compare the protective effects of ambrisentan, a selective endothelin typeA receptor antagonist, and bosentan, a dual endothelin typeA/B receptor antagonist, on experimental renal ischemia reperfusion injury. METHOD: The study sample consisted of 21 female rats, which were divided into 3 groups: Control, Ambrisentan and Bosentan. For the ischemia-reperfusion injury model, left‑kidney nephrectomy was performed after sacrificing the animals...
2020: Bratislavské Lekárske Listy
Xue Xiao, Tong Yao, Shuaishuai Du, Jin Wang, Pinging Yan, Yali Lei, Lei Cao, Zhenxing Shen, Yongxiao Cao
Exposure to air pollution is associated with the incidence of respiratory diseases. The present study evaluated the pulmonary vascular system injury by chronic real-time particulate matter (PM10 ) exposure and investigated the underlying mechanisms. Rats were exposed to PM10 or filtered air for 2 to 4 months using a whole body exposure system, and intraperitoneally injected with the MEK1/2 inhibitor U0126. Right heart catheterization and myography were performed to detect lung function and pulmonary vascular reactivity, respectively...
July 22, 2020: Toxicology and Applied Pharmacology
Ewa Kwiatkowska, Katarzyna Stefańska, Maciej Zieliński, Justyna Sakowska, Martyna Jankowiak, Piotr Trzonkowski, Natalia Marek-Trzonkowska, Sebastian Kwiatkowski
Preeclampsia (PE) is a disorder that affects 3-5% of normal pregnancies. It was believed for a long time that the kidney, similarly to all vessels in the whole system, only sustained endothelial damage. The current knowledge gives rise to a presumption that the main role in the development of proteinuria is played by damage to the podocytes and their slit diaphragm. The podocyte damage mechanism in preeclampsia is connected to free VEGF and nitric oxide (NO) deficiency, and an increased concentration of endothelin-1 and oxidative stress...
July 17, 2020: International Journal of Molecular Sciences
Malik Bisserier, Natasha Pradhan, Lahouaria Hadri
Pulmonary arterial hypertension (PAH) is a progressive and fatal lung disease of multifactorial etiology. Most of the available drugs and FDA-approved therapies for treating pulmonary hypertension attempt to overcome the imbalance between vasoactive and vasodilator mediators, and restore the endothelial cell function. Traditional medications for treating PAH include the prostacyclin analogs and receptor agonists, phosphodiesterase 5 inhibitors, endothelin-receptor antagonists, and cGMP activators. While the current FDA-approved drugs showed improvements in quality of life and hemodynamic parameters, they have shown only very limited beneficial effects on survival and disease progression...
June 30, 2020: Reviews in Cardiovascular Medicine
Robert Weishar, Ming-Song Lee, Gianluca Fontana, Peiman Hematti, Wan-Ju Li
Human mesenchymal stem/stromal cells (hMSCs) reside in a vascularized microenvironment and experience a host of blood vessel secretions, including endothelin-1 (ET1). Previously, our group has demonstrated improved induction of osteogenesis and chondrogenesis in hMSCs through an ET1-induced increase in production of anabolic factors. The current study explores effects of ET1 on catabolic factors secreted by hMSCs during chondrogenesis and osteogenesis. Cell proliferation and extracellular matrix (ECM) deposition were also explored...
August 20, 2020: Biochemical and Biophysical Research Communications
Selina M Garcia, Lindsay M Herbert, Benjimen R Walker, Thomas C Resta, Nikki L Jernigan
Although voltage-gated Ca2+ channels (VGCC) are a major Ca2+ entry pathway in vascular smooth muscle cells (VSMCs), several other Ca2+-influx mechanisms exist and play important roles in vasoreactivity. One of these is store-operated Ca2+ entry (SOCE), mediated by an interaction between STIM1 and Orai1. Although SOCE is an important mechanism of Ca2+ influx in non-excitable cells (cells that lack VGCC); there is debate regarding the contribution of SOCE to regulate VSMC contractility and the molecular components involved...
2020: PloS One
Sharifa Alzahrani, Sadeem M Ajwah, Sumayyah Yasser Alsharif, Eman Said, Mohamed El-Sherbiny, Sawsan A Zaitone, Mohamed Al-Shabrawey, Nehal M Elsherbiny
Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus that leads to significant vision loss. Isoliquiritigenin (ISL) is a bioactive flavonoid found in the root of licorice with reported anti-oxidant and anti-inflammatory activities. In the present study, we evaluated the effect of ISL administration on diabetes-induced retinal injury. Diabetes was induced in male Sprague-Dawley rats using single intraperitoneal streptozotocin (STZ, 50 mg/kg) injection. Diabetic rats showed up-regulated retinal miR-195, reduced retinal levels of SIRT-1, and increased levels of oxidative stress, nuclear factor-κB (NF-κB), inflammatory cytokines, and endothelin-1...
July 22, 2020: Naunyn-Schmiedeberg's Archives of Pharmacology
Francesco P Boeno, Thiago R Ramis, Samuel V Munhoz, Juliano B Farinha, Cesar E J Moritz, Rodrigo Leal-Menezes, Jerri L Ribeiro, Demetra D Christou, Alvaro Reischak-Oliveira
OBJECTIVE: The current randomized controlled trial tested the hypothesis that both aerobic training and dynamic resistance training will improve inflammation, endothelial function and 24-h ambulatory blood pressure (ABP) in middle-aged adults with hypertension, but aerobic training would be more effective. METHODS: Forty-two hypertensive patients on at least one antihypertensive medication (19 men/23 women; 30-59 years of age) were randomly assigned to 12 weeks of supervised aerobic training (n = 15), resistance training (n = 15) or a nonexercise control (n = 12) group...
July 15, 2020: Journal of Hypertension
Chang-Meng Wu, Lei Zheng, Qian Wang, Yan-Wei Hu
Cell senescence is a fundamental mechanism of aging and appears to play vital roles in the onset and prognosis of cardiovascular disease, fibrotic pulmonary disease, liver disease and tumor. Moreover, an increasing body of evidence shows that cell senescence plays an indispensable role in the formation and development of atherosclerosis. Multiple senescent cell types are associated with atherosclerosis, senescent human vascular endothelial cells participated in atherosclerosis via regulating the level of endothelin-1 (ET-1), nitric oxide (NO), angiotensin II and monocyte chemoattractant protein-1 (MCP-1), senescent human vascular smooth muscle cells-mediated plaque instability and vascular calcification via regulating the expression level of BMP-2, OPN, Runx-2 and inflammatory molecules, and senescent macrophages impaired cholesterol efflux and promoted the development of senescent-related cardiovascular diseases...
July 21, 2020: Clinical Chemistry and Laboratory Medicine: CCLM
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