In the rat larynx, plasma exudation and edema formation were studied b
y light and electron microscopy after i.v. injections of the mast cell
activator compound 48/80, substance P, and capsaicin. The morphologic
al effects of substance P and capsaicin on connective tissue mast cell
s in vivo were also examined. Of the drugs tested, only compound 48/80
degranulated the connective tissue mast cells. All drugs induced a su
bepithelial plasma exudation in the subglottic region, with edema in t
he lamina propria and widened intraepithelial intercellular spaces, th
ough the tight junction regions seemed intact. In the epiglottis, 10 m
in after compound 48/80 injection, there was edema in the lamina propr
ia on the Lingual side, with an intact and tight epithelial lining. No
morphological sign of edema was found in the epiglottis after injecti
on of substance P or capsaicin. The pronounced effect found in the epi
glottic region after compound 48/80 injection was due to the release o
f mediators such as histamine and 5-hydroxytryptamine from the connect
ive tissue mast cells. This study supports the belief that substance P
in vivo mediates an increased vascular permeability by a direct effec
t on the blood vessels - a mechanism distinct from mast cell degranula
tion.