title: Effect of antiasthma drugs on microvascular leakage in guinea pig airways.
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 micrograms/kg) inhibited PAF-induced changes in dye leakage in larynx and main bronchi; at 80 and 160 micrograms/kg, significant inhibition was observed in all airways studied. This effect was reversed by phentolamine (2.5 mg/kg) or prazosin (100 micrograms/kg). By contrast, albuterol (20 to 320 micrograms/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 micrograms/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.
authors.affiliation: Department of Thoracic Medicine, Cardiothoracic Institute, London, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Boschetto
authors.forename: N M
authors.initials: NM
authors.lastname: Roberts
authors.forename: D F
authors.initials: DF
authors.lastname: Rogers
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000503:physiopathology; D006168:Guinea Pigs; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D010972:Platelet Activating Factor; D005070:Evans Blue