Effect of Antiasthma Drugs on Microvascular Leakage in Guinea Pig Airways

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Abstract
We have studied the effect 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 .mu.g/kg) inhibited PAF-induced changes in dye leakage in larynx and main bronchi; at 80 and 160 .mu.g/kg, significant inhibiton was observed in all airways studied. This effect was reversed by phentolamine (2.5 mg/kg) or prazosin (100 .mu.g/kg). By contrast, albuterol (20 to 320 .mu.g/kg) and aminophyline (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 .mu.g/kg), although inhibition was not dose dependent. These results suggest that the antiedema effect of epinephrine may be due to vasoconstriction rather than to a direct effect on endothelial cell contractility and that neither .beta.-agonists nor theophylline have an inhibitory effect. The inhibitory effect of epinephrine on airway microvascular leakage may have therapeutic implications for asthma.