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    Eosinophils

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    Effect of anti-asthma drugs on microvascular leakage in guinea-pig airways

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    We have studied the effects of intravenous epinephrine, albuterol, verapamil, and aminophylline on airway microvascular leakage in guinea pigs. Microvascular leakage was induced by platelet-activating factor (PAF; 50 ng/kg intravenously), which acts directly on venular endothelial cells, and measured by quantifying extravasation of Evans blue (EB) dye. Epinephrine (20 μg/kg) inhibited PAF-induced changes in dye leakage in larynx and main bronchi; at 80 and 160 μg/kg, significant inhibition was observed in all airways studied. This effect was reversed by phentolamine (2.5 mg/kg) or prazosin (100 μg/kg). By contrast, albuterol (20 to 320 μg/kg) and aminophylline (12.5 to 50 mg/kg) failed to inhibit dye leakage at any dose studied. Verapamil inhibited PAF-increased leakage in larynx, main bronchi, and intrapulmonary airways at the lowest dose tested (125 μg/kg), although inhibition was not dose dependent. These results suggest that the antiedema effect of epinephrine may be due to vasocon..

    Corticosteroid inhibition of airway microvascular leakage

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    We studied the effect of dexamethasone on microvascular leakage (using Evans blue dye as a marker of plasma exudation) induced in rat airways by platelet-activating factor (PAF). Intravenously administered PAF caused a dose-related increase in plasma leakage over the range 0.1 to 1 micrograms/kg. At 500 ng/kg PAF, the response was maximal in the extrapulmonary airways examined with increases in leakage above those in control animals of 312% in the larynx, 295% in the trachea, and 167% in the main bronchi. A maximal response was not achieved in the intrapulmonary airways at the doses of PAF tested: at 1 microgram/kg the increase was 206% above that in control animals. Dexamethasone, given by intraperitoneal injection 24 h and 4 h before PAF at a dose of 0.2 mg/kg on each occasion, partially inhibited leakage induced by PAF (1 microgram/kg) in all airway levels studied by 43 to 65%. At each level the tissue concentration of dye was reduced to a value that was significantly (p less than 0.05) different from either PAF or control values. We also determined whether a high dose (8 mg/kg) of dexamethasone given intraperitoneally would inhibit plasma leakage of dye induced by either PAF or antigen-challenge of sensitized rats. When given 4 h before antigen, dexamethasone completely prevented allergen-induced leakage in the airways showing significant leakage (larynx, trachea, and intrapulmonary airways). Similarly, dexamethasone (4 h before) partially inhibited PAF-induced leakage in the trachea and main bronchi. In summary, in rat airways, both low and high doses of dexamethasone markedly inhibit mediator-induced plasma exudation
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