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The majority of airway sensory innervation originates from afferent neurons whose somata reside in vagal (nodose and jugular) ganglia. Using guinea pigs immunized with chick ovalbumin, we have discovered that airway inflammation provokes phenotypic changes in the tachykinin responsiveness of nodose neurons. Bath application of substance P (SP; 0.1 to 10 microM) to nodose neurons isolated from guinea pigs with normal uninflamed airways did not elicit measurable changes in resting electrophysiological properties. In sharp contrast, 80% of nodose neurons isolated 24 h after in vivo aerosolized antigen challenge of the airway were depolarized by 100 nM SP. Inhalation of a nonantigenic protein did not evoke the expression of SP responses. Pharmacological analysis revealed that SP responses unmasked by airway inflammation were mediated by neurokinin-2 (NK-2) tachykinin receptors. There are several potential mechanisms for transduction of an "unmasking signal" from the inflamed airway to vagal afferent somata. The vagus nerve may relay the signal, either through anterograde transport and/or nerve impulse activity. Alternatively, a signal generated by airway inflammation may be carried by the circulation to the nodose ganglia. Unilateral vagotomy significantly reduced the percentage of SP-responsive neurons compared with intact controls, suggesting that the vagus nerve is required for unmasking of NK-2 responses.

The effect of alpha-trinositol (D-myoinositol-1,2,6-triphosphate) on edema formation and capillary permeability in neurogenically induced inflammatory edema was investigated in rat trachea. Interstitial fluid pressure (Pif) was studied, since increased negativity of Pif contributes to edema formation in this situation. alpha-Trinositol was used because it inhibits edema formation, capillary leakage, and increased negativity of Pif in burn-injured skin. Pif was measured with sharpened glass capillaries (3 to 7 microns) connected to a servocontrolled counterpressure system after circulatory arrest (induced by intracardiac injection of saturated potassium chloride in pentobarbital anesthesia). This was done in order to avoid the edema formation associated with inflammatory reactions, which will raise interstitial fluid volume and Pif, causing the underestimation of an increased negativity of Pif. Neurogenic inflammation induced by electrical-field stimulation of the left vagal nerve (10 V, 20 Hz, 0.5 ms) lowered Pif from -1.4 +/- 0.6 mm Hg to -8.4 +/- 2.1 mm Hg (p < 0.01). Corresponding numbers after the intravenous administration of alpha-trinositol (40 mg/kg) before stimulation were -1.2 +/- 0.4 and -1.4 +/- 0.4 mm Hg, respectively (p > 0.05). Another series of animals with intact circulation was used to study the effect of vagal nerve stimulation and alpha-trinositol on edema formation (total tissue water and extravascular 51Cr-ethylenediamine tetraacetic acid-[EDTA] space) and albumin extravasation. These parameters increased significantly after vagal nerve stimulation, while intravenous alpha-trinositol (40 and 120 mg/kg), as given above, significantly attenuated this increase. Thus, alpha-trinositol prevented a lowering of Pif and the edema formation accompanying neurogenic inflammation in rat trachea.