Neurogenic Inflammation in the Airways: I. Neurogenic Stimulation Induces Plasma Protein Extravasation into the Rat Airway Lumen

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Abstract
Activation of sensory nerves in rodent airways results in microvascular permeability and edema formation, presumably due to release of vasoactive neuropeptides from the nerve endings. We examined the possibility that neurogenic stimulation may also induce movement of plasma proteins into the airway lumen. Neurogenic plasma protein extravasation (PPE) was induced in Sprague-Dawley rats by electrical stimulation of both vagal nerves (EVS) at 10 V, 5 ms, 20 Hz. After 90 s of EVS, histologic examination showed Monastral blue B, a macromolecular tracer, extravasated within the endothelium of vessels in the subepithelial layer of the tracheobronchial mucosa. In animals given 125I-labeled albumin intravenously, PPE was quantitated as microliters of plasma deposited into the airways, lung, and tracheobronchial (TB) and bronchoalveolar (BA) lavages. One minute of EVS induced an immediate increase in PPE in the tracheal (+117%) and bronchial wall (+125%) but not in the peripheral lung. There was a concomitant increase in the 125I-labeled albumin recovered from both TB fluid (net increase, 1.29 .mu.l of plasma = +259%) and BA fluid (net increase, 2.79 .mu.l of plasma = +107%). In addition, both total protein and endogenous albumin concentrations in TB fluid also increased after EVS. The albumin/total protein ratio (the albumin percentage) in TB lavages was also significantly increased (1.4 .times., 1.7 .times., and 2.5 .times. in three separate experiments, respectively), indicating the vascular origin of the increased luminal proteins. Neither cholinergic (atropine) nor adrenergic blockade (phentolamine + propranolol) influenced EVS-induced PPE into the airway walls or movement of radiolabeled albumin into the airway lumen. However, atropine did significantly reduce EVS-induced increases in endogenous proteins in the TB fluids. Our results indicate that neurogenic stimulation induces a noncholinergic, nonadrenergic PPE into the TB wall, and there is a concomitant, in part atropine-sensitive, movement of plasma proteins into the airway lumen.