ET receptors are involved in the febrile response induced by high dose of bacterial endotoxin.

Previous studies have demonstrated that endothelin-1 (ET-1) is involved in the febrile response induced by lipopolysaccharide (LPS) in male and female rats. This peptide induces fever acting on ET receptors in the central nervous system. However, during sepsis, endothelinergic ET receptors in the brain also exert an important role reducing the mortality of the animals. The present study evaluated the participation of ET receptors in the febrile response induced by different doses LPS in rats. Male Wistar rats were treated with the ET receptor antagonist BQ123 before or after the injection of a low dose (10 μg/kg) or a high dose (200 μg/kg) of LPS intraperitoneally. The febrile response was evaluated. The treatment with BQ123, in both protocols did not change the febrile response induced by the lower dose of LPS. The pre-treatment with BQ123 also did not significantly change the febrile response induced by a higher dose of LPS but the post-treatment with the antagonist abolished the febrile response induced by this dose of LPS. These results suggest that even though ET receptors are not recruited in the febrile response induced by lower doses of LPS, they are involved in the febrile response induced by high doses of this stimulus.