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MECHANISM OF THE PRO‐INFLAMMATORY ACTIVITY OF SYMPATHOMIMETIC AMINES IN THERMIC OEDEMA OF THE RAT PAW
Author(s) -
GREEN K.L.
Publication year - 1974
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1974.tb08568.x
Subject(s) - chemistry , bradykinin , isoprenaline , phenoxybenzamine , endocrinology , medicine , phentolamine , histamine , mepyramine , propranolol , kinin , pharmacology , stimulation , biochemistry , antagonist , receptor
1 Thermic oedema induced by heating rat paws at 46.5°C was potentiated by local injection of adrenaline, noradrenaline or high doses of isoprenaline. The pro‐inflammatory effect of sympathomimetic amines was antagonized by phenoxybenzamine or phentolamine but not by propranolol. 2 The subcutaneous space of heated rat paws was perfused with Tyrode solution and the perfusate collected and assayed for bradykinin, bradykininogen, kinin‐forming activity and kininase activity. When adrenaline (0.5 μg/ml) was included in the perfusion fluid, kininase activity of the perfusate was increased by 76% and free bradykinin reduced by 46%. 3 Increased vascular permeability induced by injection of bradykinin or kallikrein was reduced by adrenaline or noradrenaline, but isoprenaline had no significant effect. 4 Pretreatment with soya bean trypsin inhibitor (SBTI) or heparin did not antagonize the pro‐inflammatory effect of adrenaline or thermic oedema per se . 5 Potentiation of thermic oedema similar to that induced by sympathomimetic amines was obtained by injecting paws with vasopressin prior to heating, or by applying a ligature to stop blood flow to the paw for the first 15 min of heating. 6 Thermistor probes inserted beneath the paw skin showed that sympathomimetic amines increased the internal temperature of heated paws. This was significant, as small changes in temperature had a marked effect on the development of thermic oedema. 7 It is suggested that sympathomimetic amines potentiate thermic oedema of rat paws heated at 46.5°C by reducing blood flow to the paw, thereby causing a greater rise in paw temperature and consequently greater injury.