Leakage of macromolecules from guinea‐pig tracheobronchial microcirculation. Effects of allergen, leukotrienes, tachykinins, and anti‐asthma drugs

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Abstract
The tracheobronchial mucosa of anaesthetized guinea‐pigs (normal or sensitized with ovalbumin to produce IgE and IgG antibodies) was superfused (0.02 ml min‐1, 5 min) with saline, mediators, and (in sensitized animals) ovalbumin via a catheter atraumatically introduced orally. The intravascular blood pool and amount of macromolecules in excised trachea and adjoining main bronchi were quantified by measuring erythrocytes, that had been labelledin vivowith99Tcm, and analysing for FITC‐dextran, MW = 70,000, that had been given i. v. Extravasation of macromolecules was determined as the analysed total content minus the calculated intravascular content of FITC‐dextran. Capsaicin 0.1 nmol extravasated 223 μg of FITC‐dextran per g wet weight of airway tissue (P< 0.001). Substance P 0.1 nmol, 41 μg g‐1(P> 0.05); substance P 0.3 nmol, 142 μg g_1(P< 0.001); eledoisine 0.1 nmol, 101 μg g_1(P> 0.01); ovalbumin 0.1 μg, 179 μg g‐1(P< 0.001); LTC4, 0.2 pmol, 180 μgg‐1(P< 0.001); LTD40.2 pmol 223 μg ml‐1(P< 0.001). Bronchi and trachea were similarly affected by these agents. Prior superfusion. (0.02 ml min‐1, 30 min) with terbutaline 0.06 nmol, enprofylline 12 nmol, or lidocaine 6 nmol significantly reduced the effect of capsaicin. Enprofylline also reduced significantly the effect of LTC4. The degree of extrevasation in this study was smaller than could be detected by changes in tissue wet to dry weight ratios. The present data support the view that tracheobronchial vasculr permeability to macro‐molecules is subject to physiological and pharmacological control.