A STUDY OF NEUROKININS AND OTHER EDEMA-INDUCING MEDIATORS AND MECHANISMS IN THERMAL-INJURY

1. Mechanisms involved in the plasma extravasation observed following thermal injury of rat dorsal skin were investigated. 2. Heat applied t o the dorsal skin of anaesthetized rats by a temperature-controlled sk in heater (1 cm diameter) for 5 min induced temperature-dependent plas ma protein extravasation at 48-48.5 degrees C, measured for up to 4 h following initiation of heat. 3. A tachykinin NK1 receptor antagonist (SR140333), a bradykinin B-2 receptor antagonist (HOE140) and a cycle- oxygenase inhibitor (indomethacin), when given as cotreatments prior t o the selected measurement period, markedly suppressed oedema formatio n observed over 0-1 h (P < 0.05) but not that observed over 3-4 h afte r injury. 4. These results indicate that although neurokinins, bradyki nin and cyclo-oxygenase products may be important for the early respon se to thermal injury, they do not appear to play an important role in the ongoing oedema response. 5. Neutrophils accumulate at the inflamma tory site by 4 h after thermal injury, Therefore, the effect of deplet ion of circulating neutrophils by a rat anti-neutrophil antiserum on o edema formation over the 0-4 h period was investigated, The results sh ow that oedema formation was similar in control and antineutrophil-tre ated rats. 6. In conclusion, the data from the present study indicate that neuropeptides as well as other vasoactive mediators play a role i n the acute plasma extravasation observed after thermal injury, but no t in the ongoing inflammatory injury, Neutrophils, despite their prese nce at sites of thermal injury, do not appear to be involved in mediat ing the oedema formation observed up to 4 h after thermal injury.