NEUROGENIC INFLAMMATION IN RAT TRACHEA IS ACCOMPANIED BY INCREASED NEGATIVITY OF INTERSTITIAL FLUID PRESSURE

The present experiments were performed to investigate whether neurogen ic inflammation in rat trachea (with edema formation and protein extra vasation when the circulation is intact) induced by electrical field s timulation of neuropeptide-containing C fibers in the vagal nerve is a ccompanied by increased negativity of interstitial fluid pressure (P(i f)). Increased negativity of P(if) in the trachea occurs in dextran an aphylaxis and mast cell degranulation and facilitates edema formation under these circumstances. Experiments were performed after circulator y arrest had been induced in pentobarbital anesthesia to prevent edema formation, which will raise P(if) and potentially cause underestimati on of an increased negativity of P(if). After induction of circulatory arrest, the vagal nerve was isolated and placed in a stimulating elec trode. The trachea was then exposed and covered with mineral oil, and measurement of P(if) was started as soon as possible thereafter. P(if) was measured with sharpened glass capillaries (tip diameter, 3 to 7 m um) connected to a servocontrolled counterpressure system. P(if) in th e control group (n = 12) did not change throughout the observation per iod. Electrical stimulation of the left vagal nerve caused P(if) to fa ll in all experiments, from - 1.1 +/- 1.1 mm Hg in the control conditi on to an average of -10.6 +/- 3.4 mm Hg (n = 9, P < .01). In some expe riments, a continuous recording of P(if) was obtained, showing that th e reduction of P(if) started within 30 seconds after onset of stimulat ion to reach and later remain at a stable level within a few minutes. The experimental protocol was repeated after the C fibers had been nea rly depleted of neuropeptides with capsaicin. In this group (n=7), vag al nerve stimulation had no effect on P(if), which averaged -0.8 +/- 0 .9 and -0.08 +/- 1.7 mm Hg before and after stimulation, respectively (P > .05). Mast cell degranulation with C48/80 (n = 5) and polymyxin B (n = 6) resulted in P(if) of -5 to -6 mm Hg, and subsequent vagal ner ve stimulation was without effect on P(if). This could suggest that th e increased negativity of P(if) occurring in the initial phase of neur ogenic inflammation in rat trachea involves mast cell degranulation. F inally, the presence and localization of immunoreactive calcitonin gen e-related peptide (CGRP) and substance P were studied in transverse se ctions of trachea. Normally, the neuropeptides were typically located right under the mucosa, adjacent to mast cells and blood vessels. Caps aicin resulted in near depletion of immunoreactive calcitonin gene-rel ated peptide and substance P. In conclusion, electrical field stimulat ion of the vagal C fibers in rat trachea for the first time provides e xperimental evidence for a functional innervation of loose connective tissue, causing increased negativity of P(if).