MECHANISM OF THE PRO‐INFLAMMATORY ACTIVITY OF SYMPATHOMIMETIC AMINES IN THERMIC OEDEMA OF THE RAT PAW

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Abstract
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. 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%. Increased vascular permeability induced by injection of bradykinin or kallikrein was reduced by adrenaline or noradrenaline, but isoprenaline had no significant effect. Pretreatment with soya bean trypsin inhibitor (SBTI) or heparin did not antagonize the pro‐inflammatory effect of adrenaline or thermic oedema per se. 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. 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. 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.