Neurogenic inflammation in the rat trachea. II. Identity and distribution of nerves mediating the increase in vascular permeability.
This study addresses the question of whether increased vascular permeability, which is a prominent feature of neurogenic inflammation in the respiratory tract, is mediated by sensory axons that end near venules in the airway mucosa. In these experiments, neurogenic inflammation was produced in the tracheal and bronchial mucosa of atropine-treated Long-Evans rats by electrical stimulation of the left or right superior laryngeal nerve and/or cervical vagus nerve. The particulate tracer Monastral blue was injected intravenously to localize the sites of increased vascular permeability, and microspectrophotometry was used to measure the amount of extravasated Monastral blue in the trachea and thereby quantify the increase in vascular permeability. In some rats, selective denervations were made to locate the cell bodies of neurons that mediate the increase in vascular permeability; in others, fluorescence immunohistochemistry and quantitative electron microscopic methods were used to determine which structures in the tracheal mucosa are innervated by these neurons. The study revealed that the vagally mediated increase in vascular permeability was sudden, transient (half-life = 2.4 min) and restricted to venules. Stimulation of the left or right superior laryngeal nerve increased the permeability of venules in the extrathoracic trachea, whereas stimulation of either vagus nerve increased vascular permeability in the intrathoracic trachea and bronchi. All nerves had bilateral effects in the trachea, but the vagus nerves had largely unilateral effects in the bronchi. Neurons that mediated the increase in venular permeability had their cells bodies in the jugular (superior sensory) ganglion of the vagus nerve or rostral portion of the nodose (inferior sensory) ganglion. Preganglionic autonomic vagal neurons in the brain stem were not essential for this increase in venular permeability. Few nerves identifiable by substance P-immunohistochemistry or electron microscopy were located near the affected venules, and no nerves were within 1 micron of the walls of venules. However, the epithelium and arterioles of the airway mucosa were densely innervated. All intraepithelial nerves were within 0.1 micron of epithelial cells, and at least two-thirds of nerves near arterioles were within 1 micron of the vessel walls. We conclude that the increase in venular permeability associated with neurogenic inflammation in the trachea and bronchi of rats is mediated by sensory axons that travel in the vagus nerves and superior laryngeal nerves.(ABSTRACT TRUNCATED AT 400 WORDS)
McDonald
D M
DM
Cardiovascular Research Institute, University of California, San Francisco 94143.
Mitchell
R A
RA
Gabella
G
G
Haskell
A
A
D000818:Animals; D002199:Capillary Permeability; D004558:Electric Stimulation; D005260:Female; D007249:Inflammation / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D008854:Microscopy, Electron; D009475:Neurons, Afferent / Q000473:pathology* / Q000502:physiology; D051381:Rats; D012140:Respiratory Tract Diseases / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D014132:Trachea / Q000098:blood supply / Q000294:innervation* / Q000473:pathology; D014630:Vagus Nerve / Q000473:pathology / Q000503:physiopathology