Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo

Abstract

The purpose of this study was to determine whether dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux from the in situ hamster cheek pouch and, if so, whether this response is specific. By using intravital microscopy, we found that an aqueous extract of grain sorghum dust elicited significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (FITC-dextran; mol mass, 70 kDa) from the in situ hamster cheek pouch (P < 0.05). This response was significantly attenuated by dexamethasone (10 mg/kg iv). Dexamethasone also attenuated substance P-induced leaky site formation and increase in clearance of FITC-dextran from the cheek pouch but had no significant effects on adenosine-induced responses. Dexamethasone had no significant effects on arteriolar diameter in the cheek pouch. On balance, these data indicate that dexamethasone attenuates grain sorghum dust extract- and substance P-induced increases in macromolecular efflux from the in situ hamster cheek pouch in a specific fashion.

E. coli lipopolysaccharide attenuates adenosine A1 receptor-mediated increase in plasma exudation from the hamster cheek pouch

“…The hamster cheek pouch is an established animal model to study the effects of pro-inflammatory mediators, including LPS, adenosine and its receptor subtype agonists, bradykinin and substance P, on macromolecular efflux from post-capillary venules in situ and the mechanisms underlying these phenomenon [1, 6, 9–14, 25, 26]. In this model, solute efflux is determined by two reproducible parameters, leaky site formation and clearance of FITC-dextran, thereby providing quantitative appraisal of macromolecular transport across post-capillary venules in cheek pouch during experimental interventions.…”

“…Adult male golden Syrian hamsters (120–140 g body weight) were used in these studies as previously described in our laboratory and by other investigators [1, 6, 9–14]. Each animal was anesthetized with pentobarbital sodium (6 mg/100 g body weight i.p.).…”

“…To visualize the microcirculation of the cheek pouch, we used a method previously described in our laboratory and by other investigators [1, 6, 9–14]. Briefly, the left cheek pouch was spread gently over a small plastic base plate and an incision was made in the skin to expose the cheek pouch membrane.…”

“…Fluorescence microscopy was accomplished with the aid of filters that matched the spectral characteristics of FITC-dextran [1, 6, 9–14]. Macromolecular leakage was determined by extravasation of FITC-dextran, which appeared as fluorescent “spots” or leaky sites around post-capillary venules.…”

“…We and others have previously shown that bradykinin and substance P each increases plasma exudation from the intact hamster cheek pouch in receptor-specific fashion [9–14]. The experimental design was identical to that outlined above except that bradykinin or substance P (each, 0.5 μM) was suffused for 5 min onto intact cheek pouches of naïve hamsters and hamsters treated with LPS (77 μg/kg, i.p.)…”