Endothelin-1 inhibits PAF-induced paw oedema and pleurisy in the mouse.

Abstract

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.

• Authors: M G Henriques, G A Rae, R S Cordeiro, T J Williams
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 106 Issue 3 Pg. 579-82 (Jul 1992) ISSN: 0007-1188 [Print] England
• PMID: 1504742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Endothelins
• Platelet Activating Factor

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Edema (chemically induced, prevention & control)
• Endothelins (pharmacology)
• Female
• Foot
• Male
• Mice
• Platelet Activating Factor (pharmacology)
• Pleurisy (chemically induced, prevention & control)