Peptidase modulation of noncholinergic vagal bronchoconstriction and airway microvascular leakage

1991 ◽  
Vol 70 (6) ◽  
pp. 2730-2735 ◽  
Author(s):  
J. O. Lotvall ◽  
K. Tokuyama ◽  
C. G. Lofdahl ◽  
A. Ullman ◽  
P. J. Barnes ◽  
...  
Keyword(s):  
Nerve Stimulation ◽  
Evans Blue ◽  
Enzyme Inhibitors ◽  
Airflow Obstruction ◽  
Neutral Endopeptidase ◽  
Blue Dye ◽  
Enalapril Maleate ◽  
Evans Blue Dye ◽  
Microvascular Leakage ◽  
Degradative Enzymes

We investigated whether inhibition of neutral endopeptidase 24.11 (NEP) and/or angiotensin-converting enzyme (ACE) modifies vagally induced nonadrenergic noncholinergic (NANC) airflow obstruction and airway microvascular leakage as measured by extravasation of Evans blue dye (intravenous) in anesthetized guinea pigs. We gave phosphoramidon to inhibit NEP and enalapril maleate or captopril to inhibit ACE. Animals pretreated with inhaled phosphoramidon (7.5 or 75 nmol), enalapril maleate (87 or 870 nmol), or captopril (350 nmol) reached higher peak lung resistance (RL) values (14.3 +/- 2.7, 15.7 +/- 3.8, 16.7 +/- 3.8, 11.4 +/- 1.6, and 24.6 +/- 3.5 cmH2O.ml-1.s, respectively) than saline-treated animals (5.9 +/- 1.1; P less than 0.05) after bilateral vagus nerve stimulation (5 Hz, 10 V, 10 ms, 150 s). Intravenous phosphoramidon (1 mg/kg), but not intravenous captopril (6 mg/kg), potentiated peak RL (22.9 +/- 6.9 and 7.1 +/- 1.5 cmH2O.ml-1.s, respectively). Vagal nerve stimulation (1 and 5 Hz) increased the extravasation of Evans blue dye in tracheobronchial tissues compared with sham-stimulated animals, but this was not potentiated by inhaled enzyme inhibitors or intravenous captopril. However, intravenous phosphoramidon significantly augmented the extravasation of Evans blue dye in main bronchi and intrapulmonary airways. We conclude that degradative enzymes regulate both NANC-induced airflow obstruction and airway microvascular leakage.

Airflow obstruction after substance P aerosol: contribution of airway and pulmonary edema

1990 ◽  
Vol 69 (4) ◽  
pp. 1473-1478 ◽  
Author(s):  
J. O. Lotvall ◽  
R. J. Lemen ◽  
K. P. Hui ◽  
P. J. Barnes ◽  
K. F. Chung
Keyword(s):  
Substance P ◽  
Pulmonary Edema ◽  
Evans Blue ◽  
Guinea Pigs ◽  
Airflow Obstruction ◽  
Maximum Effect ◽  
Blue Dye ◽  
Evans Blue Dye ◽  
Microvascular Leakage ◽  
Lung Resistance

We have studied the effects of aerosolized substance P (SP) in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation. In addition, we have examined the concomitant formation of airway microvascular leakage and lung edema. Increasing breaths of SP (1.5 mg/ml, 1.1 mM), methacholine (0.15 mg/ml, 0.76 mM), or 0.9% saline were administered to tracheostomized and mechanically ventilated guinea pigs. Lung resistance (RL) increased dose dependently with a maximum effect of 963 +/- 85% of baseline values (mean +/- SE) after SP (60 breaths) and 1,388 +/- 357% after methacholine (60 breaths). After repeated hyperinflations, methacholine-treated animals returned to baseline, but after SP, mean RL was still raised (292 +/- 37%; P less than 0.005). Airway microvascular leakage, measured by extravasation of Evans Blue dye, occurred in the brain bronchi and intrapulmonary airways after SP but not after methacholine. There was a significant correlation between RL after hyperinflation and Evans Blue dye extravasation in intrapulmonary airways (distal: r = 0.89, P less than 0.005; proximal: r = 0.85, P less than 0.01). Examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with SP compared with those treated with methacholine or saline. We conclude that the inability of hyperinflation to fully reverse changes in RL after SP may be due to the formation of both airway and pulmonary edema, which may also contribute to the deterioration in RL.

Relationship between airway microvascular leakage, edema, and baseline airway functions

1998 ◽  
Vol 84 (1) ◽  
pp. 77-81
Author(s):  
Melissa Matheson ◽  
Ann-Christine Rynell ◽  
Melissa McClean ◽  
Norbert Berend
Keyword(s):  
Evans Blue ◽  
Airway Resistance ◽  
Respiratory Physiology ◽  
Blue Dye ◽  
Wall Area ◽  
Evans Blue Dye ◽  
Microvascular Leakage ◽  
Airway Function ◽  
Significant Difference ◽  
Before And After

Matheson, Melissa, Ann-Christine Rynell, Melissa McClean, and Norbert Berend. Relationship between airway microvascular leakage, edema, and baseline airway functions. J. Appl. Physiol. 84(1): 77–81, 1998.—This study was designed to examine the relationship among microvascular leakage, edema, and baseline airway function. Microvascular leakage was induced in the airways of anesthetized, tracheostomized New Zealand White rabbits ( n = 22) by using nebulized N-formyl-methionyl-leucyl-phenylalanine (10 mg) and was measured in the trachea by using the Evans blue dye technique. Airway wall thickness was assessed morphometrically in the right main bronchus after Formalin fixation at a pressure of 25 cmH2O. Areas calculated included the mucosal wall area, the adventitial wall area, the total wall area, and the percentage of total wall area consisting of blood vessels. A neutrophil count was also performed by analyzing numbers of cells in both the mucosal wall area and the adventitial wall area. Airway function was assessed before and 30 min after challenge with N-formyl-methionyl-leucyl-phenylalanine by determining airway resistance, functional residual capacity, specific airway resistance, and flow-volume and pressure-volume curves (after paralysis of the animals with suxamethonium). The concentration of Evans blue dye in tracheal tissue ranged from 31.3 to 131.2 μg. There was a significant correlation between this concentration and both the adventitial wall area ( P < 0.01) and mucosal neutrophil numbers ( P < 0.005). There was no correlation between Evans blue concentration and either blood vessel area or changes in respiratory physiology parameters before and after challenge. There was no significant difference between any respiratory physiology measurements before and after challenge. We conclude that an increase in microvascular leakage correlates with airway edema in the adventitia; however, these airway changes have no significant effect on airway elastic or resistive properties.

Role of peptidases and NK1 receptors in vascular extravasation induced by bradykinin in rat nasal mucosa

1993 ◽  
Vol 74 (5) ◽  
pp. 2456-2461 ◽  
Author(s):  
C. Bertrand ◽  
P. Geppetti ◽  
J. Baker ◽  
G. Petersson ◽  
G. Piedimonte ◽  
...  
Keyword(s):  
Nasal Mucosa ◽  
Evans Blue ◽  
Sensory Nerve ◽  
Ace Inhibition ◽  
Neutral Endopeptidase ◽  
Blue Dye ◽  
Nk1 Receptor ◽  
Evans Blue Dye ◽  
Neurokinin 1 ◽  
Evans Blue Extravasation

We used Evans blue dye to assess the effects of bradykinin on vascular extravasation in nasal mucosa of pathogen-free F344 rats. There was a dose-dependent increase in Evans blue extravasation when bradykinin was delivered by topical instillation in the nose (doses, 25–100 nmol). Only the highest intravenous doses (2 and 5 mumol/kg) of bradykinin caused increased extravasation. When bradykinin was delivered by either route, its effect on extravasation was exaggerated by pharmacological inhibition of the enzymes neutral endopeptidase (NEP) and kininase II [angiotensin-converting enzyme (ACE)]. When bradykinin was instilled locally, the effect of NEP inhibition was predominant; when bradykinin was injected intravenously, the effect of ACE inhibition was predominant. The mechanism of extravasation also varied with the mode of bradykinin delivery: when bradykinin was instilled locally in the nose, the selective neurokinin 1 (NK1) receptor antagonist CP-96,345 markedly inhibited the response, whereas it had no effect on Evans blue extravasation when bradykinin was injected intravenously. We conclude that bradykinin causes dose-related increases in Evans blue dye extravasation in the nose and that these effects are exaggerated when NEP and ACE are inhibited. Topically instilled bradykinin causes vascular extravasation to a large extent via NK1 receptor stimulation, thus suggesting a major role for tachykinins released from sensory nerve endings.

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.

scholarly journals A Study of the Pathogenesis and Prevention of Central Pontine Myelinolysis in a Rat Model

2006 ◽  
Vol 34 (3) ◽  
pp. 264-271 ◽  
Author(s):  
Q-H Ke ◽  
T-B Liang ◽  
J Yu ◽  
S-S Zheng
Keyword(s):  
Hypertonic Saline ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Central Pontine Myelinolysis ◽  
Brain Barrier ◽  
Blue Dye ◽  
Evans Blue Dye ◽  
Pontine Myelinolysis ◽  
Demyelinating Lesions ◽  
Central Pontine

The development of central pontine myelinolysis was studied in rats. Severe hyponatraemia was induced using vasopressin tannate and 2.5% dextrose in water and then rapidly corrected with hypertonic saline alone, hypertonic saline and dexamethasone simultaneously, or hypertonic saline plus dexamethasone 24 h later. The permeability of the blood-brain barrier was evaluated using the extravasation of Evans blue dye and the expression of inducible nitric oxide synthase (iNOS) in the brain was examined using Western blot analysis. Histological sections were examined for demyelinating lesions. In rats receiving hypertonic saline alone, Evans blue dye content and expression of iNOS began to increase 6 and 3 h, respectively, after rapid correction of hyponatraemia and demyelinating lesions were seen. When dexamethasone was given simultaneously with hypertonic saline, these increases were inhibited and demyelinating lesions were absent. These effects were lost if dexamethasone injection was delayed. Disruption of the blood-brain barrier and increased iNOS expression may be involved in the pathogenesis of central pontine myelinolysis, and early treatment with dexamethasone may help prevent the development of central pontine myelinolysis.

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