Endothelin-1 inhibits PAF-induced paw oedema and pleurisy in the mouse.
1. The current study analyses the effects of endothelin-1 (ET-1) on paw oedema and pleurisy induced by platelet activating factor (PAF) and other inflammatory agents in the mouse. 2. Combined subplantar injection of ET-1 (0.5 pmol/paw) did not modify oedema caused by histamine (1 to 100 mumol/paw), 5-hydroxytryptamine (1 to 100 mumol/paw) or bradykinin (1 to 100 nmol/paw) but markedly inhibited the response to PAF (0.95 to 3.8 nmol/paw). The selective action of ET-1 against PAF-induced (1.9 nmol/paw) oedema was dose-dependent, reaching a maximum at 0.5 pmol/paw and lasted up to 2 h. 3. ET-1 (0.5 pmol/paw) also inhibited paw oedema (3-4 h) caused by zymosan (500 micrograms/paw). In contrast, it did not modify either the early (1-4 h) or late (48-72 h) phases of the oedematogenic response to carrageenin (300 micrograms/paw), when given either together with or 24 h after the carrageenin. 4. Intrathoracic injection of PAF (1.9 nmol/cavity) induced pleurisy characterized by an increase in pleural exudate volume, and in accumulation of Evans Blue which was maximal at 30 min and lasted up to 4 h. When injected together with PAF, ET-1 (0.5 pmol/cavity) virtually abolished PAF-induced pleurisy. 5. It is concluded that ET-1 is a potent inhibitor of PAF-induced inflammation in the mouse. Its mechanism of anti-inflammatory action in this species, in contrast to what has been found in other species, does not appear to derive from its potent vasoconstrictor properties as ET-1, at the doses used, failed to affect oedematogenic responses to other inflammatory mediators.
Henriques
M G
MG
Department of Physiology and Pharmacodynamics, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Rae
G A
GA
Cordeiro
R S
RS
Williams
T J
TJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D005528:Foot; D008297:Male; D051379:Mice; D010972:Platelet Activating Factor / Q000494:pharmacology; D010998:Pleurisy / Q000139:chemically induced / Q000517:prevention & control*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016232:Endothelins; D010972:Platelet Activating Factor