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Vascular Pharmacology

Hassan Dehaini, Manal Fardoun, Haissam Abou Saleh, Ahmed El-Yazbi, Assaad A Eid, Ali H Eid
Cardiovascular disease (CVD) continues to be the leading cause of death worldwide. The effect of estrogen on these diseases has been assessed in in vitro and in vivo models, as well as in observational studies. Collectively, these studies alluded to a cardiovasculo-protective effect of estrogen. However, comprehensive clinical investigation failed to produce concrete proof of a cardiovascular protective effect for hormone replacement therapy (HRT), let alone rule out potential harm. These seemingly paradoxical effects of estrogen were explained by the 'theory of timing and opportunity'...
September 15, 2018: Vascular Pharmacology
Mateusz Tomczyk, Izabela Kraszewska, Jozef Dulak, Agnieszka Jazwa-Kusior
Upon myocardial infarction (MI) immune system becomes activated by extensive necrosis of cardiomyocytes releasing intracellular molecules called damage-associated molecular patterns. Overactive and prolonged immune responses are likely to be responsible for heart failure development and progression in patients surviving the ischemic episode. Heme oxygenase-1 (HO-1) plays a crucial role in heme degradation and in this way releases carbon monoxide, free iron, and biliverdin. This stress-inducible enzyme is induced by various oxidative and inflammatory signals...
September 10, 2018: Vascular Pharmacology
Damian Kloska, Aleksandra Kopacz, Aleksandra Piechota-Polanczyk, Witold Nowak, Jozef Dulak, Alicja Jozkowicz, Anna Grochot-Przeczek
Aging is the most critical risk factor for the development of cardiovascular diseases and their complications. Therefore, the fine-tuning of cellular response to getting older is an essential target for prospective therapies in cardiovascular medicine. One of the most promising targets might be the transcription factor Nrf2, which drives the expression of cytoprotective and antioxidative genes. Importantly, Nrf2 expression correlates with potential lifespan in rodents. However, the effect of Nrf2 activity in vascular diseases might be ambiguous and strongly depend on the cell type...
August 28, 2018: Vascular Pharmacology
Natália A Gonzaga, Wanessa M C Awata, Gabriel T do Vale, Katia C Marchi, Jaqueline J Muniz, Jose E Tanus-Santos, Carlos R Tirapelli
AIM: We investigated the consequences of acute ethanol intake on the anti-contractile effect of perivascular adipose tissue (PVAT). METHODS: The effects of a single dose of ethanol (1 g/kg; p.o. gavage) on the vascular function were assessed within 30 min in male Wistar rats. RESULTS: Ethanol decreased the relaxation induced by acetylcholine and increased the contraction induced by phenylephrine in endothelium-intact, but not in endothelium-denuded aortas without PVAT...
August 26, 2018: Vascular Pharmacology
Gemma Vilahur, Manuel Gutiérrez, Monika Arzanauskaite, Guiomar Mendieta, Soumaya Ben-Aicha, Lina Badimon
Platelets are endowed with a repertoire of surface receptors that enable them to adhere, activate and aggregate upon vascular injury. Platelet adhesion is governed by the interaction between vascular collagen and GPIb-IX-V and GPVI-FcRγ complexes. Platelet kinases downstream 14-3-3ζ-bound GPIb and the FcRγ ITAM domain enable the activation of PLC-γ2 whereas the engagement of soluble agonists (predominantly ADP, TXA2 and thrombin) with Gq-protein coupled receptor trigger PLC-β activation. Once activated, PLC-γ2/β induces the generation of second messengers IP3 and DAG...
August 18, 2018: Vascular Pharmacology
Jana Pourová, Iveta Najmanová, Marie Vopršalová, Thomas Migkos, Veronika Pilařová, Lenka Applová, Lucie Nováková, Přemysl Mladěnka
SCOPE: The flavonoid quercetin reduces arterial blood pressure in animals and humans but the mechanisms remains elusive. The aim of this study was to test the activity of flavonoid microbial metabolites, which can participate on the final vasorelaxant effect. METHODS AND RESULTS: Both ex vivo (isolated rat thoracic aorta and mesenteric artery) and in vivo (normotensive and spontaneously hypertensive rats) approaches were used in this study. 4-methylcatechol and 3,4-dihydroxyphenylacetic acid (DHPA) had greater vasorelaxant effects on mesenteric artery than 3-(3-hydroxyphenyl)propionic acid, the previously reported metabolite with vasorelaxant effect...
August 14, 2018: Vascular Pharmacology
Eithne M Maguire, Stuart W A Pearce, Qingzhong Xiao
During atherosclerosis, the gradual accumulation of lipids into the subendothelial space of damaged arteries results in several lipid modification processes followed by macrophage uptake in the arterial wall. The way in which these modified lipoproteins are dealt with determines the likelihood of cholesterol accumulation within the monocyte-derived macrophage and thus its transformation into the foam cell that makes up the characteristic fatty streak observed in the early stages of atherosclerosis. The unique expression of chemokine receptors and cellular adhesion molecules expressed on the cell surface of monocytes points to a particular extravasation route that they can take to gain entry into atherosclerotic site, in order to undergo differentiation into the phagocytic macrophage...
August 13, 2018: Vascular Pharmacology
Lai Yen Fong, Chin Theng Ng, Yoke Keong Yong, Muhammad Nazrul Hakim, Zuraini Ahmad
Endothelial hyperpermeability represents an initiating step in early atherosclerosis and it often occurs as a result of endothelial barrier dysfunction. Asiatic acid, a major triterpene isolated from Centella asiatica (L.) Urban, has previously been demonstrated to protect against tumor necrosis factor (TNF)-α-induced endothelial barrier dysfunction. The present study aimed to investigate the mechanisms underlying the barrier protective effect of asiatic acid in human aortic endothelial cells (HAECs). The localization of F-actin, diphosphorylated myosin light chain (diphospho-MLC), adherens junctions (AJs) and tight junctions (TJs) was studied using immunocytochemistry techniques and confocal microscopy...
August 13, 2018: Vascular Pharmacology
John S Smeda, Danielle Watson, Jennifer Stuckless, Amit Negandhi
We assessed the ability of poststroke losartan and captopril treatment to attenuate hematoma expansion and plasma extravasation after intracerebral hemorrhagic stroke in Kyoto-Wistar stroke-prone hypertensive rats (SHRsp). Cerebrum volume, herniation and surface areas exhibiting new and old hemorrhages and albumin extravasation were measured prior to and after stroke and following 30 and 60 days of post-stroke losartan or captopril treatment in Evans Blue dye perfused brains. Lesion morphology was studied in serial sections...
August 13, 2018: Vascular Pharmacology
Philipp Schineis, Peter Runge, Cornelia Halin
The lymphatic system has long been known to serve as a highway for migrating leukocytes from peripheral tissue to draining lymph nodes (dLNs) and back to circulation, thereby contributing to the induction of adaptive immunity and immunesurveillance. Lymphatic vessels (LVs) present in peripheral tissues upstream of a first dLN are generally referred to as afferent LVs. In contrast to migration through blood vessels (BVs), the detailed molecular and cellular requirements of cellular traffic through afferent LVs have only recently started to be unraveled...
August 7, 2018: Vascular Pharmacology
Katarzyna Sztuka, Daria Orszulak-Michalak, Magdalena Jasińska-Stroschein
A systematic review and meta-analysis was performed to test candidate therapeutic approaches in pulmonary hypertension (PH). The efficacy of 522 interventions with >200 unregistered drugs was tested on 7254 animals. We propose a modified formula to assess meta-data that concerns the contribution of PH animal model to the denoted efficacy of tested agents. The measure of efficacy expressed as a response ratio for right ventricle systolic pressure was 0.48 (95% CI, 0.46-0.50; P < 0.00001), mean pulmonary artery pressure was 0...
November 2018: Vascular Pharmacology
P J Hohensinner, J Baumgartner, B Ebenbauer, B Thaler, M B Fischer, K Huber, W S Speidl, J Wojta
BACKGROUND AND AIMS: Macrophages are versatile immune cells involved in tissue degradation and remodeling. Proinflammatory macrophages have the highest capacity of matrix degradation and proteolysis. Within atherosclerotic lesions, proinflammatory macrophages are associated with unstable plaques. Statins have been demonstrated to increase plaque stability. Possible changes of polarized macrophage tissue degradation behavior under statin treatment are currently unknown. METHODS: Polarized macrophages were tested in vitro for matrix degradation capacity with or without statin treatment...
November 2018: Vascular Pharmacology
S Zullino, F Buzzella, T Simoncini
Nitric oxide (NO) is a key regulator of both maternal and fetal homeostasis during pregnancy, facilitating the maternal cardio-vascular changes, fetal development and growth and adaptation to extrauterine life. Dysfunction of the NO system during pregnancy is associated to placental and vascular-related diseases such as hypertensive disorders of pregnancy (HDP) and intrauterine growth restriction (IUGR). Emerging therapeutic strategies involving NO precursors, NO donors, natural derivatives or pharmacological modulators of the NO system seem hold promise for the treatment of such conditions of pregnancy...
November 2018: Vascular Pharmacology
Thiago Sardinha de Oliveira, Lais Moraes de Oliveira, Lanussy Porfiro de Oliveira, Rafael Menezes da Costa, Rita de Cássia Tostes, Raphaela de Castro Georg, Elson Alves Costa, Núbia de Souza Lobato, Fernando Paranaiba Filgueira, Paulo César Ghedini
Estrone (E1) produces remarkable vascular effects, including relaxation, modulation of proliferation, apoptosis and cell adhesion. This study investigated the role of estrogen receptors and endothelial signaling pathways in the vascular relaxation promoted by E1. Aortic rings from male Wistar rats (250-300 g) were contracted with phenylephrine and stimulated with graded concentrations of E1. The concentration-dependent relaxation induced by E1 was abolished after removal of the endothelium or incubation with the estrogen receptor antagonist ICI 182,780...
November 2018: Vascular Pharmacology
Zi Ping Leong, Yoshiaki Hikasa
Sorafenib reverses pulmonary arterial hypertension (PAH) and cardiopulmonary remodeling (CPR), but the effects of toceranib are unknown. This study investigated anti-remodeling effects and determined optimal doses of toceranib and sorafenib on monocrotaline (MCT)-induced PAH and CPR in rats. MCT-treated rats were orally treated with a 14-day course of sorafenib (10, 30, or 100 mg/kg), toceranib (1, 3, or 10 mg/kg), or water. Both sorafenib and toceranib significantly reversed the right ventricular (RV) hypertrophy at 10 mg/kg, but only sorafenib significantly improved the RV systolic and mean pressures...
November 2018: Vascular Pharmacology
Jaspreet Kaur, Harman S Mattu, Kamaljit Chatha, Harpal S Randeva
Adipose tissue, initially known only for storing excess fat, produces a number of active cytokine-like hormones, collectively known as adipokines or adipocytokines. These molecules are further known to elicit auto-, para- and endocrine functions in the body. In healthy bodies, the cardiovascular endothelium maintains vascular health by critically controlling the interplay between various factors. However, in diseased states such as obesity, owing to numerous metabolic malfunctions, this vascular homeostasis is disrupted...
November 2018: Vascular Pharmacology
Youhai Li, Natalia Lapina, Nina Weinzierl, Lisbeth Bonde, Ebbe Boedtkjer, Rudolf Schubert, Han Moshage, Paulus Wohlfart, Lothar Schilling
Alterations in the retinal microvessel (RMV) compartment occurring in systemic disease states such as diabetes may eventually contribute to blindness. To specifically address the pathophysiological role of the microvasculature we developed a new method for RMV bulk isolation from individual rats. The extraction procedure performed in the cold throughout takes less than one hour. Slight modifications enable isolation of brain microvessels (BMVs) for comparison. Microscopically, RMVs and BMVs consisted mainly of capillaries of good structural integrity...
November 2018: Vascular Pharmacology
Paul A Lederer, Tingting Zhou, Weiguo Chen, Yulia Epshtein, Huashan Wang, Biji Mathew, Jeffrey R Jacobson
Acute lung injury (ALI) is characterized by endothelial barrier disruption resulting in increased vascular permeability. As focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase, is involved in endothelial cell (EC) barrier regulation, we hypothesized that FAK inhibition could attenuate agonist-induced EC barrier disruption relevant to ALI. Human lung EC were pretreated with one of three pharmacologic FAK inhibitors, PF-573,228 (PF-228, 10 μM), PF-562,271 (PF-271, 5 μM) or NVP-TAE226 (TAE226, 5 μM) for 30 min prior to treatment with thrombin (1 U/ml, 30 min)...
November 2018: Vascular Pharmacology
Brenda Lilly, Kristen Dammeyer, Sam Marosis, Patricia E McCallinhart, Aaron J Trask, Megan Lowe, Dwitiya Sawant
Cytoglobin is a widely expressed heme protein that binds oxygen, carbon monoxide and nitric oxide. Recent examination of cytoglobin in the vasculature indicates that it contributes to nitric oxide availability, which is central to normal blood vessel function through regulation of smooth muscle cell tone and physiological response. Given the potential implications of cytoglobin in vascular function, we examined how cytoglobin might be uniquely regulated in vascular smooth muscle cells. Our data demonstrate that endothelial cells can increase the expression of cytoglobin in vascular smooth muscle cells, and the induction of cytoglobin is cell contact-dependent...
November 2018: Vascular Pharmacology
Aleksandar Jurisic, Zaklina Jurisic, Eleftheria Lefkou, Joaquim Pombo, Guillermina Girardi
The increase in fetal and neonatal morbidity and mortality associated with twin pregnancies correlates with an increased risk of preterm delivery, low birth weight, and intrauterine growth restriction (IUGR). Although the pathogenesis of IUGR is unclear and thus management remains a major challenge, feto-placental blood vessels are compromised, and altered umbilical blood flow is observed. In this pilot observational study we investigated the effects of pravastatin plus l-arginine on umbilical artery (umb art) blood flow...
November 2018: Vascular Pharmacology
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