A study of neurokinins and other oedema-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 to the dorsal skin of anaesthetized rats by a temperature-controlled skin heater (1 cm diameter) for 5 min induced temperature-dependent plasma 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 B2 receptor antagonist (HOE 140) and a cyclo-oxygenase inhibitor (indomethacin), when given as cotreatments prior to the selected measurement period, markedly suppressed oedema formation observed over 0-1 h (P < 0.05) but not that observed over 3-4 h after injury. 4. These results indicate that although neurokinins, bradykinin and cyclo-oxygenase products may be important for the early response to thermal injury, they do not appear to play an important role in the ongoing oedema response. 5. Neutrophils accumulate at the inflammatory site by 4 h after thermal injury. Therefore, the effect of depletion of circulating neutrophils by a rat anti-neutrophil antiserum on oedema formation over the 0-4 h period was investigated. The results show that oedema formation was similar in control and anti-neutrophil-treated rats. 6. In conclusion, the data from the present study indicate that neuropeptides as well as other vasoactive mediators play a role in the acute plasma extravasation observed after thermal injury, but not in the ongoing inflammatory injury. Neutrophils, despite their presence at sites of thermal injury, do not appear to be involved in mediating the oedema formation observed up to 4 h after thermal injury.
Waller
J
J
Pharmacology Group, King's College, London, United Kingdom.
Siney
L
L
Hoult
J R
JR
Brain
S D
SD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D004487:Edema / Q000209:etiology*; D005334:Fever / Q000503:physiopathology*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D015320:Tachykinins / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D043782:Receptor, Bradykinin B2; D015320:Tachykinins; C085215:SR 140333; C065679:icatibant; D001920:Bradykinin