The role of ETA and ETB receptor antagonists in acute and allergic inflammation in mice

In this study, we investigated the effects of the selective ETA (BQ-123) and ETB (BQ-788) receptor antagonists for endothelin-1 (ET-1) against several flogistic agent-induced paw edema formation and ovalbumin-induced allergic lung inflammation in mice. The intraplantar injection of BQ-123, but not BQ-788, significantly inhibited carrageenan-, PAF-, ET-1- and bradykinin-induced paw edema formation. The obtained inhibitions (1 h after the inflammatory stimulus) were 79 ± 5%, 55 ± 4%, 55 ± 6% and 74 ± 4%, respectively. In carrageenan-induced paw edema, the mean ID50 value for BQ-123 was 0.77 (0.27–2.23) nmol/paw. The neutrophil influx induced by carrageenan or PAF was reduced by BQ-123, with inhibitions of 55 ± 2% and 72 ± 4%, respectively. BQ-123 also inhibited the indirect macrophage influx induced by carrageenan (55 ± 6%). However, BQ-788 failed to block the cell influx caused by either of these flogistic agents. When assessed in the bronchoalveolar lavage fluid in a murine model of asthma, both BQ-123 and BQ-788 significantly inhibited ovalbumin-induced eosinophil recruitment (78 ± 6% and 71 ± 8%), respectively. Neither neutrophil nor mononuclear cell counts were significantly affected by these drugs. Our findings indicate that ETA, but not ETB, selective ET-1 antagonists are capable of preventing the acute inflammatory responses induced by carrageenan, PAF, BK and ET-1. However, both ETA and ETB receptor antagonists were found to be effective in inhibiting the allergic response in a murine model of asthma.