The Role of eNOS in Vascular Permeability in ENU-Induced Gliomas

2009 ◽  
pp. 277-282 ◽  
Author(s):  
S. Bulnes ◽  
E. G. Argandoña ◽  
H. Bengoetxea ◽  
O. Leis ◽  
N. Ortuzar ◽  
...  
Keyword(s):  
Vascular Permeability

scholarly journals The G protein βγ subunit mediates reannealing of adherens junctions to reverse endothelial permeability increase by thrombin

2009 ◽  
Vol 206 (12) ◽  
pp. 2761-2777 ◽  
Author(s):  
Nebojsa Knezevic ◽  
Mohammad Tauseef ◽  
Tracy Thennes ◽  
Dolly Mehta
Keyword(s):  
Vascular Permeability ◽  
Focal Adhesion ◽  
Inflammatory Mediator ◽  
Adherens Junctions ◽  
Endothelial Permeability ◽  
Endothelial Barrier ◽  
Dependent Manner ◽  
Permeability Increase ◽  
Lung Vascular Permeability

The inflammatory mediator thrombin proteolytically activates protease-activated receptor (PAR1) eliciting a transient, but reversible increase in vascular permeability. PAR1-induced dissociation of Gα subunit from heterotrimeric Gq and G12/G13 proteins is known to signal the increase in endothelial permeability. However, the role of released Gβγ is unknown. We now show that impairment of Gβγ function does not affect the permeability increase induced by PAR1, but prevents reannealing of adherens junctions (AJ), thereby persistently elevating endothelial permeability. We observed that in the naive endothelium Gβ1, the predominant Gβ isoform is sequestered by receptor for activated C kinase 1 (RACK1). Thrombin induced dissociation of Gβ1 from RACK1, resulting in Gβ1 interaction with Fyn and focal adhesion kinase (FAK) required for FAK activation. RACK1 depletion triggered Gβ1 activation of FAK and endothelial barrier recovery, whereas Fyn knockdown interrupted with Gβ1-induced barrier recovery indicating RACK1 negatively regulates Gβ1-Fyn signaling. Activated FAK associated with AJ and stimulated AJ reassembly in a Fyn-dependent manner. Fyn deletion prevented FAK activation and augmented lung vascular permeability increase induced by PAR1 agonist. Rescuing FAK activation in fyn−/− mice attenuated the rise in lung vascular permeability. Our results demonstrate that Gβ1-mediated Fyn activation integrates FAK with AJ, preventing persistent endothelial barrier leakiness.

scholarly journals Enhancement of vascular permeability by specific activation of protease-activated receptor-1 in rat hindpaw: a protective role of endogenous and exogenous nitric oxide

1999 ◽  
Vol 126 (8) ◽  
pp. 1856-1862 ◽  
Author(s):  
Atsufumi Kawabata ◽  
Ryotaro Kuroda ◽  
Hiroyuki Nishikawa ◽  
Toshiharu Asai ◽  
Kazuo Kataoka ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Permeability ◽  
Protective Role ◽  
Protease Activated Receptor 1 ◽  
Exogenous Nitric Oxide

scholarly journals The role of central and peripheral D2R receptors in the mechanism of colonic vascular permeability during experimental colitis in rats

2017 ◽  
Vol 22 (1) ◽  
pp. 39-43
Author(s):  
A. Prysiazhniuk ◽  
T. Dovbynchuk ◽  
B. Kopiyak ◽  
G. Tolstanova
Keyword(s):  
Ulcerative Colitis ◽  
Vascular Permeability ◽  
Experimental Colitis ◽  
Inbred Rats ◽  
Simultaneous Activation ◽  
Colitis Ulcerative ◽  
Joint Injections ◽  
Positive Effect ◽  
Experimental Ulcerative Colitis

We investigated the involvement of central and peripheral D2 dopaminergic receptors in the mechanism of vascular permeability in rat's colon during experimental ulcerative colitis. Ulcerative colitis was induced in male white inbred rats by 6 % iodoacetamide enema. For the investigation of central and peripheral D2R, separate and joint injections of D2R antagonist domperidone (2 mg/100 g, per os) and D2R agonist quinpirole (1 mg/100 g, per os) were applied. Central D2R were destroyed by neurotoxin injection – 6OHDA. Colonic vascular permeability was measured by colonic extravasation of 1,5 % Evans blue. It was observed that blockade of peripheral D2R decreased colonic vascular permeability, while simultaneous activation of central D2R and inhibition of peripheral D2R have additive positive effect in prevention of increased colonic vascular permeability during experimental colitis.

Granulocytes mediate the increase in pulmonary vascular permeability after thrombin embolism

1983 ◽  
Vol 54 (6) ◽  
pp. 1489-1495 ◽  
Author(s):  
M. V. Tahamont ◽  
A. B. Malik
Keyword(s):  
Vascular Permeability ◽  
Control Group ◽  
Base Line ◽  
Protein Ratio ◽  
Pulmonary Vascular Permeability ◽  
Pulmonary Capillary ◽  
Cellular Factors ◽  
Pulmonary Embolization ◽  
Lung Lymph

We examined the effect of pulmonary embolization with microthrombi on the lung vascular permeability to proteins and the role of platelets and granulocytes as putative cellular factors in mediating the alterations in permeability. Anesthetized artificially ventilated sheep were prepared with lung lymph fistulas. Pulmonary embolization was induced using thrombin. Pulmonary vascular resistance (PVR) was increased approximately threefold from baseline. Pulmonary lymph flow (Qlym) increased 2 h after thrombin, but the lymph-to-plasma protein ratio (L/P) did not change significantly from base line. Raising the pulmonary capillary pressure (Pc) by inflating a left atrial balloon produced a large increase in Qlym but no change in L/P, indicating a permeability-increasing effect of thrombin. Reduction of platelet count with antiplatelet serum before thrombin also produced an increase in Qlym without a change in L/P. Raising Pc in this group resulted in changes comparable with those in the control group, i.e., increased Qlym without a change in L/P. In contrast to both control and platelet-depleted groups, reduction of the granulocyte count with hydroxyurea did not affect Qlym or L/P after thrombin. Raising Pc in this group increased Qlym but decreased L/P, indicating normal capillary sieving of proteins. Therefore embolization of pulmonary vessels with microthrombi increases pulmonary vascular permeability, and the increase is mediated by granulocytes.

Fibronectin deficiency and intestinal transvascular fluid balance during bacteremia

1982 ◽  
Vol 242 (4) ◽  
pp. H557-H564
Author(s):  
B. C. Dillon ◽  
T. M. Saba
Keyword(s):  
Vascular Permeability ◽  
Fluid Balance ◽  
Protein Concentration ◽  
Lymph Flow ◽  
Fluid Flux ◽  
Fluid Filtration ◽  
Coated Particles ◽  
P Protein ◽  
Small Intestinal

Reticuloendothelial (RE) clearance dysfunction, which can be induced by opsonic fibronectin deficiency, has been correlated with organ failure during sepsis. We investigate the role of opsonic fibronectin deficiency and RE blockade in modulating alterations in intestinal transvascular fluid balance induced by Pseudomonas bacteremia using an isolated, innervated, and autoperfused canine small intestinal segment. Intravenous infusion of gelatin-coated particles was used to induce fibronectin deficiency and RE blockade. Lymph flow and lymph/plasma (L/P) protein concentration ratios were stable following intravenous challenge with bacteria or gelatin-coated particles. In contrast, lymph flow increased and L/P ratio decreased significantly when bacteremia coexisted with particle-induced opsonic fibronectin deficiency and RE blockade. This elevation in lymph flow and decline in L/P ratio was associated with normal vascular permeability to albumin, IgG, and IgM. The increase in intestinal fluid flux during bacteremia with RE blockade appears to be due to an increase in microvascular hydrostatic pressure and not to an increase in vascular permeability. These findings emphasize a potentially important role for fibronectin and associated RE system function as determinants of fluid filtration during sepsis.

scholarly journals Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability

Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2167-2173 ◽  
Author(s):  
Luke H. Hoeppner ◽  
Kathryn N. Phoenix ◽  
Karl J. Clark ◽  
Resham Bhattacharya ◽  
Xun Gong ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Real Time ◽  
Molecular Mechanisms ◽  
Negative Regulator ◽  
Transgenic Zebrafish ◽  
Genetic Studies ◽  
In Vivo Models ◽  
Ischemic Diseases

AbstractVEGF induces vascular permeability (VP) in ischemic diseases and cancer, leading to many pathophysiological consequences. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of VP do not exist. In the present study, we report a heat-inducible VEGF transgenic zebrafish (Danio rerio) model through which VP can be monitored in real time. Using this approach with morpholino-mediated gene knock-down and knockout mice, we describe a novel role of phospholipase Cβ3 as a negative regulator of VEGF-mediated VP by regulating intracellular Ca2+ release. Our results suggest an important effect of PLCβ3 on VP and provide a new model with which to identify genetic regulators of VP crucial to several disease processes.

Ischemia-induced vascular changes: role of xanthine oxidase and hydroxyl radicals

1983 ◽  
Vol 245 (2) ◽  
pp. G285-G289 ◽  
Author(s):  
D. A. Parks ◽  
D. N. Granger
Keyword(s):  
Hydroxyl Radical ◽  
Dimethyl Sulfoxide ◽  
Xanthine Oxidase ◽  
Vascular Permeability ◽  
Hydroxyl Radicals ◽  
Vascular Injury ◽  
Oxygen Radicals ◽  
Intestinal Ischemia ◽  
Xanthine Oxidase Inhibitor

The results of previous studies indicate that oxygen-derived free radicals are responsible for the increased vascular permeability produced by 1 h of intestinal ischemia. The aims of this study were 1) to test the hypothesis that the enzyme xanthine oxidase is the source of oxygen radicals in the ischemic bowel and 2) to assess the role of the hydroxyl radical in the ischemia-induced vascular injury. The capillary osmotic reflection coefficient was estimated from lymphatic protein flux data in the cat ileum for the following conditions: ischemia, ischemia plus pretreatment with allopurinol (a xanthine oxidase inhibitor), and ischemia plus pretreatment with dimethyl sulfoxide (a hydroxyl radical scavenger). The increased vascular permeability produced by ischemia was largely prevented by pretreatment with either allopurinol or dimethyl sulfoxide. These findings support the hypothesis that xanthine oxidase is the source of oxygen radicals produced during ischemia. The results also indicate that hydroxyl radicals, derived from the superoxide anion, are primarily responsible for the vascular injury associated with intestinal ischemia.

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