We determined the endogenous
histamine concentration in the subplantar space of rat hind paws using an in vivo microdialysis technique. A microdialysis probe was implanted into the rat hind paw and the
histamine content in
dialysates was measured by high performance liquid chromatography-fluorometry. In wild type (+/+) rats, the
histamine output (basal level 25.7 +/- 0.9 pmol/ml) increased 115-, 199- and 426-fold rapidly after subplantar injection of
compound 48/80 at doses of 0.5, 5 and 50 microg/paw, respectively. In genetically mast cell-deficient (Ws/Ws) rats, the basal level of
histamine was one third of that obtained from +/+ rats, and was not increased by
compound 48/80 injection. With this treatment, marked, dose dependent, but relatively gradual development of the paw
edema was found in +/+ rats. However, no
edema formation was observed in Ws/Ws rats. Histological observations showed neither mast cells nor
edema to be present in the paw skin of Ws/Ws rats. These findings indicate the critical role of
histamine as a trigger for the development of
edema in vivo. In addition, Ws/Ws rats will provide important information as to the roles of mast cells in the inflammatory response.