Angiotensin-(1−7) improves tail skin heat loss and increases the survival of rats with polymicrobial sepsis

Abstract

Sepsis is a serious syndrome, characterized by the excessive release of inflammatory mediators and thermoregulatory changes, being fever the most common sign. However, despite the importance of Angiotensin (Ang)-(1−7) in controlling the inflammation, the role of the peptide in the febrile response and mortality in animals submitted to experimental model of sepsis is still not clear. In this way, we evaluate the effect of continuous infusion of Ang-(1−7) in inflammatory response, thermoregulation and in mortality of Wistar male rats submitted to colonic ligation puncture (CLP). Before CLP surgery, the infusion pumps (Ang-(1−7), 1.5 mg/mL or saline) were inserted into the abdominal cavity and maintained for 24 h. CLP rats showed a febrile response starting from 3 h after and persisted until the 24th hour of experiment. Continuous treatment with Ang-(1−7) attenuated the febrile response and reestablished the euthermia 11 h after CLP, until the end of experiment, which coincided with an increased heat loss index (HLI). This effect was associated with a decrease in production of pro-inflammatory mediators in liver, white adipose tissue (WAT) and hypothalamus. Moreover, an increase in norepinephrine (NE) content in interscapular brown adipose tissue (iBAT) was observed in CLP animals, which was attenuated with treatment with Ang-(1−7), and decreased mortality in CLP animals treated with Ang-(1−7). Taken together, the present study demonstrates that continuous infusion treatment with Ang-(1−7) can promote a global anti-inflammatory effect, reestablishing the tail skin heat loss as a key thermo-effector function, resulting in an increased survival of animals submitted to experimental sepsis.