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.

Human urotensin-II enhances plasma extravasation in specific vascular districts in Wistar rats

2004 ◽  
Vol 82 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Gabrielle Gendron ◽  
Bryan Simard ◽  
Fernand Gobeil, Jr. ◽  
Pierre Sirois ◽  
Pedro D'Orléans-Juste ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Evans Blue ◽  
Wistar Rats ◽  
Platelet Activating Factor ◽  
Optimal Dose ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Urotensin Ii ◽  
Evans Blue Dye

Plasma extravasation (PE) was measured in adult Wistar rats by injecting Evans blue dye (EB) (20 mg kg–1) intravenously in the absence or presence of human urotensin II (U-II) (0.1–10 nmol kg–1). A consistent increase of PE was observed in specific organs (e.g., aorta, from 28.1 ± 2.4 to 74.6 ± 3.6 µg EB g–1 dry tissue; P < 0.001) after an administration of 4.0 nmol kg–1 (a preselected optimal dose) of U-II. The effects of U-II (4.0 nmol kg–1) were compared with those of endothelin-1 (ET-1) (1.0 nmol kg–1). In the thoracic aorta and pancreas, U-II was active, while ET-1 was not. The two agents were equivalent in the heart and kidney, whereas, in the duodenum, ET-1 was more active than U-II. Increases of plasma extravasation induced by U-II, but not by ET-1, were reduced after treatment with [Orn8]U-II (0.3 µmol kg–1). This latter antagonist did not show any significant residual agonistic activity in vivo in the rat. Other specific receptor antagonists for ET-1, such as BQ-123 (endothelin type A (ETA) receptor) and BQ-788 (endothelin type B (ETB) receptor), and for the platelet activating factor (PAF), such as BN50730, failed to modify the action of U-II. The present study is the first report describing the modulator roles of U-II on vascular permeability in specific organs. Moreover, the action of U-II appears specific, since it is independent of the ET-1 and PAF signalling pathways.Key words: urotensin-II, receptors antagonists, Evans blue dye, vascular permeability, rats.

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.

Neural control of vascular permeability: interactions between primary afferents, mast cells, and sympathetic efferents

1989 ◽  
Vol 62 (1) ◽  
pp. 48-58 ◽  
Author(s):  
T. J. Coderre ◽  
A. I. Basbaum ◽  
J. D. Levine
Keyword(s):  
Blood Pressure ◽  
Mast Cells ◽  
Vascular Permeability ◽  
Neural Control ◽  
Primary Afferents ◽  
Sympathetic Chain ◽  
Blue Dye ◽  
Base Line ◽  
Plasma Extravasation ◽  
Sympathetic Efferents

1. This study addressed the contribution of primary afferents, mast cells, and sympathetic efferents to the control of vascular permeability in synovial joints. Extravasation of Evans blue dye into the synovial space was measured by perfusion of the knee joint in the adult rat. Plasma extravasation (PE) was evoked by pharmacologic activation of either unmyelinated primary afferents, mast cells, or sympathetic postganglionic nerve (SPGN) terminals with acute injection of either capsaicin, compound 48/80, or 6-hydroxydopamine (6-OHDA), respectively. In otherwise untreated control rats, acute infusion of capsaicin or compound 48/80 produced a brief increase in vascular permeability; infusion of 6-OHDA produced a larger and more prolonged increase. 2. To evaluate the contribution of an interaction of different cellular elements in the joint to PE, we repeated these experiments in rats pretreated with capsaicin, compound 48/80, or 6-OHDA; administered quercetin; or surgically sympathectomized by excision of the lumbar sympathetic chain. Eliminating unmyelinated afferent nerve terminals by neonatal treatment with capsaicin only reduced the increase in PE produced by acute infusion of capsaicin. Degranulating mast cells by pretreatment with compound 48/80, or preventing the degranulation of mast cells by treatment with quercetin, reduced the increase in PE evoked by infusion of either capsaicin or compound 48/80. Finally, sympathectomy, produced by excision of the lumbar sympathetic chain or by pretreatment with 6-OHDA, significantly reduced PE elicited by acute infusion of capsaicin, compound 48/80, or 6-OHDA. 3. Neither infusing substances normally localized to sympathetic efferents nor inducing changes in blood pressure could mimic the profound increase in PE evoked by activation of sympathetic postganglionic neurons with acute infusion of 6-OHDA. Thus norepinephrine produced a significant decrease in PE, adenosine triphosphate produced only a brief increase, neuropeptide Y had no effect, and manipulating blood pressure (either up or down) had no effect on either base-line or 6-OHDA-induced PE. 4. Indomethacin treatment significantly reduced the increase in PE produced by 6-OHDA. This effect of indomethacin was reversed by the addition of prostaglandin E2 (PGE2) to the 6-OHDA in the perfusion fluid. This finding implicates prostaglandins (i.e., cyclooxygenase products of arachidonic acid metabolism) in SPGN-dependent generation of PE.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of Dose and Route Effects of Platelet Activating Factor-Induced Extravasation in the Guinea Pig

1984 ◽  
Vol 52 (01) ◽  
pp. 034-036 ◽  
Author(s):  
Dean A Handley ◽  
Ronald G Van Valen ◽  
Mary Kay Melden ◽  
Robert N Saunders
Keyword(s):  
Guinea Pig ◽  
Platelet Activating Factor ◽  
The Other ◽  
Plasma Extravasation ◽  
Dependent Manner ◽  
Naturally Occurring ◽  
Protein Rich ◽  
Dose Dependent

SummaryPlatelet-activating factor (PAF) is a naturally occurring lipid that is reported to induce vessel hyperpermeability leading to loss of protein-rich plasma (extravasation). We have quantitated the systemic extravasation effects of synthetic PAF in the guinea pig by monitoring increases in hematocrit. When given intravenously (10-170 ng/kg), PAF produced dose-dependent increases in hematocrit, with maximal hemoconcentration developing in 5-7 min. In leukopenic animals the expected hematocrit increase was reduced by 57%. PAF given intra-arterially produced the dose-dependent changes in hematocrit similar to the intravenous effects of PAF. However, PAF given intraperitoneally (10-2500 μg/kg) was 800-1100-fold less effective than the other routes and hemoconcentration continued for 30-45 min until a maximal hematocrit was observed. These results show that PAF may markedly influence extravasation of plasma in a dose and route-dependent manner.

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.

Plasma extravasation induced by neurokinins in conscious rats: receptor characterization with agonists and antagonists

1993 ◽  
Vol 71 (3-4) ◽  
pp. 217-221 ◽  
Author(s):  
Mauro Nicolau ◽  
Martin G. Sirois ◽  
Michel Bui ◽  
Gérard E. Plante ◽  
Pierre Sirois ◽  
...  
Keyword(s):  
Substance P ◽  
Urinary Bladder ◽  
Vascular Permeability ◽  
Blue Dye ◽  
Receptor Subtype ◽  
Plasma Extravasation ◽  
Functional Sites ◽  
Conscious Rats ◽  
Selective Antagonists ◽  
Selective Agonists

The purpose of the present experiments was to study the effects of various neurokinin related peptides, such as substance P, [βAla8]NKA(4–10), and [MePhe7]NKB, which are selective for NK-1, NK-2, and NK-3 functional sites, respectively, to induce plasma extravasation in rats and the effectiveness of RP 67580 and CP-96,345 (two nonpeptide NK-1 receptor selective antagonists) and SR 48968 (a nonpeptide NK-2 receptor selective antagonist) to prevent such an effect. Bolus intravenous injection of substance P (1.0 nmol/kg) into conscious rats induced extravasation of Evans blue dye (EB), a selective marker of albumin vascular permeability, in the duodenum, the stomach, the pancreas, and the urinary bladder by 50, 40, 58, and 312%, respectively; a slight increment occurred also in the ileum and the kidney but was not significant. [βAla8]NKA(4–10) (1.0 nmol/kg) increased EB extravasation in the stomach and the urinary bladder by 52 and 99%, respectively, while [MePhe7]NKB (1.0 nmol/kg) did the same in the stomach, the ileum, and the urinary bladder by 58, 50, and 79%. Pretreatment with RP 67580 (250 nmol/kg) blocked the albumin extravasation mediated by substance P in the duodenum, the pancreas, and the urinary bladder by 100, 100, and 78%, respectively. CP-96,345 (250 nmol/kg) also inhibited EB extravasation mediated by substance P in the duodenum and the pancreas by 100 and 100%, respectively, but was ineffective in the urinary bladder. Neither RP 67580 nor CP-96,345 prevented the substance P mediated extravasation in the stomach. RP 67580 and CP-96,345 did not antagonize the effects of NK-2 and NK-3 selective agonists. SR 48968 (500 nmol/kg) was inactive against substance P as well as against the NK-2 or NK-3 selective agonists. RP 67580 (250 nmol/kg), CP-96,345 (250 nmol/kg), and SR 48968 (500 nmol/kg) per se did not induce any plasma extravasation, except in the urinary bladder, where CP-96,345 and SR 48968 increased EB concentrations in the tissue. These results suggest that the effects of neurokinins on vascular permeability vary from one tissue to another. The blockade of substance P by the NK-1 receptor selective antagonists, RP 67580 and CP-96,345, suggests that NK-1 receptors play an important role in the plasma extravasation induced by substance P. However, the effects of NK-2 and NK-3 receptor selective agonists appear to be independent of activation of NK-1 receptors since they are not blocked by RP 67580 or CP-96,345. Furthermore, because the effect of [βAla8]NKA(4–10), the NK-2 selective agonist, was not abolished by SR 48968, it is suggested that it might be mediated by the NK-2 receptor subtype NK-2B, which is less sensitive to SR 48968 than is NK-2A. The contribution of NK-3 receptors to plasma extravasation could not be adequately demonstrated in the present study because NK-3 antagonists sufficiently active in vivo are not available.Key words: neurokinins, RP 67580, CP-96,345, SR 48968, vascular permeability.

Nicotine Suppression of Gustatory Responses of Neurons in the Nucleus of the Solitary Tract

2006 ◽  
Vol 96 (4) ◽  
pp. 1877-1886 ◽  
Author(s):  
Christopher T. Simons ◽  
Yves Boucher ◽  
Mirela Iodi Carstens ◽  
E. Carstens
Keyword(s):  
Monosodium Glutamate ◽  
Plasma Extravasation ◽  
Dependent Manner ◽  
Evoked Responses ◽  
Solitary Tract ◽  
Depressant Effect ◽  
Tongue Surface ◽  
Single Unit Recordings ◽  
Gustatory Neurons ◽  
Dose Dependent

This study investigated effects of nicotine applied to the tongue surface on responses of gustatory neurons in the nucleus of the solitary tract (NTS) in rats. In pentobarbital-anesthetized rats, single-unit recordings were made from NTS units responsive to one or more tastants (sucrose, NaCl, citric acid, monosodium glutamate, quinine). Application of nicotine (0.87, 8.7, or 600 mM) excited gustatory NTS units and significantly attenuated NTS unit responses to their preferred tastant in a dose-dependent manner. The depressant effect of nicotine was equivalent regardless of which tastant best excited the NTS unit. Nicotinic excitation of NTS units and depression of their tastant-evoked responses were both significantly attenuated by the nicotinic antagonist mecamylamine, which itself did not excite NTS units. In rats with bilateral trigeminal ganglionectomy, nicotine still excited nearly all NTS units but no longer depressed tastant-evoked responses. Nicotine did not elicit plasma extravasation when applied to the tongue. The results indicate that nicotine directly excites NTS units by gustatory nerves and inhibits their tastant-evoked responses by a nicotinic acetylcholine receptor-mediated excitation of trigeminal afferents that inhibit NTS units centrally.

scholarly journals Effects of esculentoside A on turnour necrosis factor production by mice peritoneal macrophages

1992 ◽  
Vol 1 (6) ◽  
pp. 375-377 ◽  
Author(s):  
Fang Jun ◽  
Zheng Qin Yue ◽  
Wang Hong Bin ◽  
Ju Dian Wen ◽  
Yi Yang Hua
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Inflammatory Mediator ◽  
Platelet Activating Factor ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Necrosis Factor ◽  
Inflammatory Effect

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments showed that it had strong anti-inflammatory effects. Tumour necrosis factor (TNF) is an important inflammatory mediator. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNF production from macrophages was altered by EsA under lipopolysaccharide (LPS) stimulated conditions. EsA was found to decrease both extracellular and cell associated TNF production in a dose dependent manner at concentrations higher than 1 μmol/l EsA. Previous studies have showed that EsA reduced the releasing of platelet activating factor (PAF) from rat macrophages. The reducing effects of EsA on the release of TNF and PAF may explain its anti-inflammatory effect.

Calcium dependence of the thrombin-induced increase in endothelial albumin permeability

1989 ◽  
Vol 66 (3) ◽  
pp. 1471-1476 ◽  
Author(s):  
H. Lum ◽  
P. J. Del Vecchio ◽  
A. S. Schneider ◽  
M. S. Goligorsky ◽  
A. B. Malik
Keyword(s):  
Endothelial Cells ◽  
Endothelial Permeability ◽  
Base Line ◽  
Dependent Manner ◽  
Extracellular Medium ◽  
Influx Rate ◽  
Before And After ◽  
Dependent Inhibition ◽  
Permeability Increase ◽  
Dose Dependent

We examined whether the increase in endothelial albumin permeability induced by alpha-thrombin is dependent on extracellular Ca2+ influx. Permeability of 125I-albumin across confluent monolayers of cultured bovine pulmonary artery endothelial cells was measured before and after the addition of 0.1 microM alpha-thrombin. In the presence of normal extracellular Ca2+ concentration ([Ca2+]o, 1000 microM), alpha-thrombin produced a 175 +/- 10% increase in 125I-albumin permeability. At lower [Ca2+]o (100, 10, 1, or less than 1 microM), alpha-thrombin caused a 140% increase in permeability (P less than 0.005). LaCl3 (1 mM), which competes for Ca2+ entry, blunted 38% of the increase in permeability. Preloading endothelial monolayers with quin2 to buffer cytosolic Ca2+ (Cai2+) produced a dose-dependent inhibition of the increase in 125I-albumin permeability. Preincubation with nifedipine or verapamil was ineffective in reducing the thrombin-induced permeability increase. A 60 mM K+ isosmotic solution did not alter base-line endothelial permeability. alpha-Thrombin increased [Ca2+]i in a dose-dependent manner and the 45Ca2+ influx rate. Extracellular medium containing 60 mM K+ did not increase 45Ca2+ influx, and nifedipine did not block the rise in 45Ca2+ influx caused by alpha-thrombin. Ca2+ flux into endothelial cells induced by alpha-thrombin does not occur through voltage-sensitive channels but may involve receptor-operated channels. In conclusion, the increase in endothelial albumin permeability caused by alpha-thrombin is dependent on Ca2+ influx and intracellular Ca2+ mobilization.

Modification of lymph during passage through the lymph node: effect of histamine

1983 ◽  
Vol 245 (4) ◽  
pp. H553-H559
Author(s):  
M. B. Maron
Keyword(s):  
Lymph Node ◽  
Flow Rate ◽  
Evans Blue ◽  
Protein Concentration ◽  
Lymph Flow ◽  
Blue Dye ◽  
Base Line ◽  
Average Flow Rate ◽  
Significant Modification ◽  
Average Flow

The possibility that histamine may cause the fluid and protein content of lymph to be altered during passage through the lymph node was evaluated using the canine perfused popliteal lymph node preparation. This preparation enables nodal perfusion via an afferent lymphatic (all other afferents are ligated) with artificial lymph of known composition and collection of the total efferent effluent for analysis of potential changes in volume and composition. In 11 dogs, the node was perfused at an average flow rate of 0.229 ml/min with artificial lymph containing 3.71 g/100 ml albumin. Under base-line conditions, there was no significant modification of the lymph as it passed through the node. The addition of histamine to the infusate (2-4 micrograms base/ml) caused the efferent lymph flow to increase to 0.295 ml/min (35.3% increases, P less than 0.05), the efferent protein concentration to increase to 4.32 g/100 ml (15.2% increases, P less than 0.05), and the efferent protein flux to increase from 8.40 to 12.86 mg/min (58.0% increases, P less than 0.05). The appearance of Evans blue dye-tagged protein and plasma protein fractions, not originally present in the lymph, in the efferent lymph at this time further indicated that the source of the added fluid and protein was the nodal vasculature. Mass balance calculations indicated that the addition of a fluid with a protein concentration of approximately 90% that of plasma to the lymph could account for the observed increases in efferent lymph flow and protein concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

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