A thromboxane mimetic, U-46619, produces plasma exudation in airways of the guinea pig

1992 ◽  
Vol 72 (6) ◽  
pp. 2415-2419 ◽  
Author(s):  
J. Lotvall ◽  
W. Elwood ◽  
K. Tokuyama ◽  
T. Sakamoto ◽  
P. J. Barnes ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Evans Blue ◽  
Blue Dye ◽  
Dependent Manner ◽  
Evans Blue Dye ◽  
Plasma Exudation ◽  
Txa2 Receptor ◽  
Txa2 Receptor Antagonist ◽  
Airway Responses ◽  
Dose Dependent

Thromboxane A2 (TxA2) has been implicated in airway responses to allergen and in the bronchial hyperresponsiveness observed in asthma. Furthermore a TxA2 receptor antagonist and a TxA2 synthase inhibitor inhibit plasma exudation in airways induced by inhaled platelet-activating factor. To evaluate whether TxA2 has any direct effect on plasma exudation in the airways, we studied the effect of a stable TxA2 mimetic (U-46619; 2, 20, and 200 nmol/kg iv) on lung resistance (RL) and Evans blue dye extravasation (marker of plasma albumin; 20 mg/kg iv) at the airway levels of trachea, main bronchi, and proximal and distal intrapulmonary airways in anesthetized, tracheostomized, and mechanically ventilated guinea pigs. Injection of U-46619 produced an immediate and marked dose-dependent increase in RL, which peaked at approximately 30 s. At the highest dose of U-46619, we also observed a later increase in RL, starting at approximately 3 min and reaching a second peak at approximately 8 min. Mean systemic blood pressure increased in a dose-dependent manner [maximum 82 +/- 8 (SE) mmHg]. U-46619 also produces dose-dependent plasma exudation, measured as Evans blue dye extravasation, at all airway levels as well as into the tracheal lumen. Airway responses to U-46619 (200 nmol/kg iv) were abolished in animals pretreated with the TxA2 receptor antagonist ICI-192605 (0.5 mg/kg iv). We conclude that U-46619, despite being a vasoconstrictor, is potent in inducing plasma exudation in airways and that this effect is mediated via a TxA2 receptor.

Effect of platelet-activating factor on airway vascular permeability: possible mechanisms

1987 ◽  
Vol 63 (2) ◽  
pp. 479-484 ◽  
Author(s):  
T. W. Evans ◽  
K. F. Chung ◽  
D. F. Rogers ◽  
P. J. Barnes
Keyword(s):  
Vascular Permeability ◽  
Evans Blue ◽  
Platelet Activating Factor ◽  
Blue Dye ◽  
Base Line ◽  
Plasma Extravasation ◽  
Dependent Manner ◽  
Lipoxygenase Inhibitor ◽  
Dose Dependent ◽  
Evans Blue Extravasation

We studied the effects of the potent inflammatory mediator, platelet-activating factor (PAF), on vascular permeability in airways (and other tissues) of guinea pigs by measuring extravasation of circulating Evans blue dye. PAF caused a dose-dependent increase in vascular permeability. At 1 ng/kg iv, PAF caused an increase in Evans blue extravasation of 220% (P less than 0.05) in the trachea, with the greatest effect at a dose of 100 ng/kg (858%; P less than 0.01). Histamine (150 micrograms/kg iv) caused a 320% increase over base line in the trachea and 200% in main bronchi; this effect was equivalent to that induced by 10 ng/kg PAF in the trachea and 1 ng/kg in main bronchi. The duration of effect of PAF was greatest in main bronchi (less than 10 min). Platelet depletion with a cytotoxic antibody, or the cyclooxygenase inhibitor, indomethacin, or the cyclooxygenase-lipoxygenase inhibitor, BW 7556, did not affect the vascular permeability response to PAF. The PAF-receptor antagonist, BN 52063, inhibited Evans blue extravasation in the airways in a dose-dependent manner, with complete inhibition at 5 mg/kg. Thus PAF-induced airway vascular leakage is mediated by specific receptors but not by products of arachidonic acid metabolism or by platelets. Increased airway microvascular leakage induced by PAF may lead to plasma extravasation and airway edema, factors that may contribute to the airway narrowing and hyperresponsiveness induced by PAF.

Tone-dependent responses of histamine in feline pulmonary vascular bed

1995 ◽  
Vol 268 (2) ◽  
pp. H653-H661 ◽  
Author(s):  
C. F. Neely ◽  
I. Matot ◽  
D. Haile ◽  
J. Nguyen ◽  
V. Batra
Keyword(s):  
Receptor Antagonist ◽  
H1 Receptor ◽  
Receptor Antagonism ◽  
H2 Receptor ◽  
Txa2 Receptor ◽  
High Doses ◽  
Txa2 Receptor Antagonist ◽  
H1 Receptor Antagonist ◽  
Spontaneously Breathing ◽  
Dose Dependent

Under conditions of controlled pulmonary blood flow and constant left atrial pressure, histamine produced tone-dependent responses in the pulmonary vascular (PV) bed of intact-chest, spontaneously breathing cats. At low, baseline PV tone, histamine produced dose-dependent increases in mean lobar arterial pressure that were antagonized by the selective histamine H1-receptor antagonist, diphenhydramine. The cyclooxygenase inhibitor, meclofenamate, and the thromboxane A2 (TxA2) receptor antagonist, SQ-29548, had no effect on these vasoconstrictor responses of histamine. After an increase in PV tone with an intralobar arterial infusion of a TxA2 mimic, U-46619, histamine produced vasodilator responses at low doses, biphasic vasodilator/vasoconstrictor responses at midrange doses, and vasoconstrictor responses at high doses. Diphenhydramine antagonized vasoconstrictor responses and the vasodilator responses of low to midrange doses and enhanced vasodilator responses of high doses of histamine at elevated PV tone. Selective H2-receptor antagonists, ranitidine and meclofenamate, and selective H3-receptor antagonist, thioperamide, did not antagonize vasodilator responses of histamine. H1- and H2-receptor antagonism was more effective in reducing the vasodilator responses of histamine at elevated PV tone than H1-receptor antagonism alone. These data support that histamine produces vasoconstrictor responses at low baseline and elevated PV tone by acting on H1 receptors that do not induce the release of vasoconstrictor prostanoids. At elevated PV tone, histamine produces vasodilation by acting on H1 receptors that are not coupled to the release of vasodilator prostaglandins and also, in part, by acting on H2 receptors.

Neuropeptide Y inhibits neurogenic inflammation in guinea pig airways

1993 ◽  
Vol 75 (1) ◽  
pp. 103-107 ◽  
Author(s):  
T. Takahashi ◽  
M. Ichinose ◽  
H. Yamauchi ◽  
M. Miura ◽  
N. Nakajima ◽  
...  
Keyword(s):  
Substance P ◽  
Neuropeptide Y ◽  
Evans Blue ◽  
Neurogenic Inflammation ◽  
Sensory Nerve ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Dependent Manner ◽  
Evans Blue Dye ◽  
Exogenous Substance

We examined the effect of neuropeptide Y (NPY) on neurogenic airway microvascular leakage. Male Dunkin-Hartley guinea pigs (250–350 g) were anesthetized with urethan (2 g/kg ip). The cervical artery and vein were cannulated for monitoring blood pressure and injecting drugs, respectively. Atropine and propranolol (each 1 mg/kg i.v.) were administered 30 min before the experiment. After pretreatment with saline (vehicle for NPY) or NPY (1–100 micrograms/kg i.v.), Evans blue dye (30 mg/kg iv) was administered. Then, bilateral vagal nerves were electrically stimulated (5 V, 7 Hz, 5-ms duration for 3 min) to induce airway plasma leakage. Airways were divided into four sections [trachea (Tr), main bronchi, central intrapulmonary airways (IPA), and peripheral IPA] and incubated in formamide (37 degrees C for 16 h). The concentration of Evans blue dye was measured by spectrophotometer. Furthermore, we examined the effect of NPY on exogenous substance P- (0.3 microgram/kg i.v.) induced plasma extravasation. Bilateral vagal stimulation significantly increased leakage of dye in Tr to peripheral IPA. NPY did not affect basal leakage but did significantly inhibit neurogenic plasma extravasation in a dose-dependent manner with maximal inhibitions of 42.3 (Tr), 67.7 (main bronchi), 38.2 (central IPA), and 26.3% (peripheral IPA) at 30 micrograms/kg. Exogenous substance P-induced plasma extravasation was not inhibited by NPY. We conclude that NPY inhibits neurogenic inflammation by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals.

Abstract TP108: Blood Occludin Level Indicates the Extent of Early Blood Brain Barrier Damage in Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Rong Pan ◽  
Kewei Yu ◽  
Theodore Weatherwax1 ◽  
Handong Zheng ◽  
Yirong Yang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Brain Barrier ◽  
Blue Dye ◽  
Dependent Manner ◽  
Cerebral Microvessels ◽  
Evans Blue Dye ◽  
Blood Brain ◽  
Junction Protein

Background and Purpose: Fear of symptomatic intracerebral hemorrhage (ICH) has been the primary reason for withholding tPA thrombolysis from acute ischemic stroke patients. Early blood brain barrier (BBB) damage is appreciated to be closely associated with post-thrombolysis ICH, while it remains a technical challenge for rapid assessment of BBB damage before tPA administration. Our recent data showed that cerebral ischemia induced rapid degradation of tight junction protein occludin in ischemic cerebromicrovessels. This study further investigates whether the cleaved occludin is released into the blood stream and how blood occludin levels correlate to the extent of ischemic BBB damage. Methods: Male Sprague Dawley rats were subjected to 1.5, 3, 4.5, 12 and 24 hours of middle cerebral artery occlusion (MCAO), followed by 5-min reperfusion. Blood samples were taken before and after MCAO. Blood occludin was assessed by ELISA. BBB permeability was measured by Evans blue dye leakage. Occludin cleavage was identified on immunoblots. Results: MCAO induced Evans blue dye leakage and blood occludin increase in a duration-dependent manner. Blood occludin increase concurrently occurred with the loss of occludin from ischemic cerebral microvessels. Western blot analysis identified two cleaved occludin fragments (31- and 55- kDa) in the blood. Lastly, blood occludin levels remained significantly higher than its basal level within the first 24 hours after MCAO onset. Conclusions: Our results indicate that blood occludin levels correlate well with the extents of BBB damage and thus may serve as a potential biomarker for evaluating the risk of hemorrhagic transformation before tPA administration.

Plasma Exudation into Airways Induced by Inhaled Platelet-Activating Factor: Effect of Peptidase Inhibition

1991 ◽  
Vol 80 (3) ◽  
pp. 241-247 ◽  
Author(s):  
Jan O. Lötvall ◽  
Wayne Elwood ◽  
Kenichi Tokuyama ◽  
Peter J. Barnes ◽  
K. Fan Chung
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Evans Blue ◽  
Guinea Pigs ◽  
Platelet Activating Factor ◽  
Neutral Endopeptidase ◽  
Blue Dye ◽  
Converting Enzyme ◽  
Evans Blue Dye ◽  
Plasma Exudation ◽  
Lung Resistance

1. To evaluate whether endogenous peptide release is involved in the airway responses to inhaled platelet-activating factor, we measured lung resistance and airway microvascular leakage in anaesthetized guinea pigs pre-treated with inhalation of either saline or a combination of the peptidase inhibitors phosphoramidon (0.1 mmol/l: 60 breaths; 7.5 nmol), to inhibit neutral endopeptidase, and captopril (4.6 mmol/l: 60 breaths; 350 nmol), to inhibit angiotensin-converting enzyme. 2. Airway microvascular leakage was determined by the albumin marker Evans Blue dye injected intravenously (20 mg/kg) before platelet-activating factor or sham challenge. 3. Inhaled platelet-activating factor induced a maximum increase in lung resistance (1.43 ± 0.33 cmH2O s−1 ml−1) which was not significantly different after pretreatment with phosphoramidon and captopril (1.44 ± 0.21 cmH2O s−1 ml−1). 4. Inhalation of platelet-activating factor caused a significant increase in extravasated Evans Blue dye at all airway levels, an effect which was not potentiated by peptidase inhibition. Similar results were obtained with dye extravasated into the airway lumen and absorbed by a filter paper placed on the tracheal mucosa. Approximately 11% of the total tracheal dye was found in the lumen. There was a high correlation between tracheal tissue and tracheal lumen Evans Blue dye (r = 0.91; P < 0.001). 5. We found a significantly lower dry to wet weight ratio in proximal intrapulmonary airways of animals exposed to platelet-activating factor, suggesting that platelet-activating factor caused airway oedema at this airway level. 6. Inhaled platelet-activating factor does not induce immediate release of peptides degraded by either neutral endopeptidase or angiotensin-converting enzyme in high enough quantities to cause bronchoconstriction. Inhaled platelet-activating factor may cause airway narrowing in guinea pigs largely due to plasma exudation into the airway wall and lumen.

Regional Deposition of Inhaled Evans Blue Dye in Mechanically Ventilated Rabbits with Air or Helium Oxygen Mixture

1998 ◽  
Vol 24 (2) ◽  
pp. 159-172 ◽  
Author(s):  
Magnus Svartengren ◽  
Patrik Skogward ◽  
Ola Nerbrink ◽  
Magnus Dahlbäck
Keyword(s):  
Evans Blue ◽  
Oxygen Mixture ◽  
Blue Dye ◽  
Mechanically Ventilated ◽  
Evans Blue Dye ◽  
Regional Deposition

scholarly journals Acoustic enhanced Evans blue dye perfusion in neurological tissues

2007 ◽  
Author(s):  
George K. Lewis Jr. ◽  
Willam L. Olbricht ◽  
George Lewis
Keyword(s):  
Evans Blue ◽  
Blue Dye ◽  
Evans Blue Dye

Flow of edema fluid into pulmonary airways

1983 ◽  
Vol 55 (4) ◽  
pp. 1262-1268 ◽  
Author(s):  
G. R. Mason ◽  
R. M. Effros
Keyword(s):  
Evans Blue ◽  
Left Atrial ◽  
Blue Dye ◽  
Edema Formation ◽  
Evans Blue Dye ◽  
Colloid Particles ◽  
Edema Fluid ◽  
Pulmonary Airways ◽  
99Mtc Sulfur Colloid

An in situ rabbit preparation was used to characterize the manner in which edema fluid enters the airways when left atrial pressures are elevated. The airways were initially filled with fluid to minimize retrograde flow of edema fluid into the alveoli. The airway solution contained 125I-albumin and in some studies [14C]sucrose, and the lungs were perfused with a comparable solution which contained albumin labeled with Evans blue dye and 99mTc-diethylenetriaminepentaacetate (DTPA) or 99mTc-sulfur-colloid particles (0.4-1.7 micron diam). After 30 min of perfusion, fluid was pumped from the airways into serial tubes. When left atrial pressures were low, there was very little transfer of labels detectable between the airway and perfusate solutions. However when left atrial pressures were increased to either 15 or 22 cmH2O, fluid entered the airways containing approximately the same concentrations of Evans blue dye and 99mTc-DTPA as those present in the perfusate. In contrast, the concentration of colloid particles averaged less than 5% perfusate concentrations, indicating that the fluid had not escaped through a tear in the barriers separating the vascular and airway compartments. Concentrations of the perfusate fluid and indicators were highest in the initial samples pumped from the airways. These observations suggest that some of the fluid entering the airways may be derived from peribronchial cuffs or that there are marked regional differences in edema formation from alveoli.

A modified bioassay for heat-stable Escherichia coli enterotoxin

1977 ◽  
Vol 23 (3) ◽  
pp. 331-336 ◽  
Author(s):  
S. Stavric ◽  
D. Jeffrey
Keyword(s):  
Escherichia Coli ◽  
Body Weight ◽  
Incubation Time ◽  
Evans Blue ◽  
Room Temperature ◽  
Blue Dye ◽  
Evans Blue Dye ◽  
Heat Stable ◽  
Stomach Distention ◽  
Time Required

Infant mice were injected orally with preparations containing Escherichia coli heat-stable enterotoxin (ST) and Evans blue dye, and incubated at 22 °C. With enterotoxin-positive samples, the stomach was distended and contained essentially all of the dye. With enterotoxin-negative samples, the stomach remained normal in size and the dye passed freely into the intestines. The time required to obtain the maximum ratio of gut weight to body weight varied from 30 to 90 min and was dependent upon the concentration of enterotoxin. Heat-labile enterotoxin (LT) had no effect during this period.Based on these findings, the mouse incubation time was reduced from 4 h to 90 min, and the heating of test samples was retained only for confirmation of ST. The location of the dye and stomach distention served as an indicator of positive responses to ST. Incubation of the mice at room temperature (22 °C) was found satisfactory.

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