ET_A 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_B receptors in the central nervous system. However, during sepsis, endothelinergic ET_A receptors in the brain also exert an important role reducing the mortality of the animals. The present study evaluated the participation of ET_A receptors in the febrile response induced by different doses LPS in rats. Male Wistar rats were treated with the ET_A 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_A 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.