Background and Goal of Study: Sepsis is a systemic inflammatory reaction that may lead to multiple organ damage, shock and death. The renin-angiotensin system consists of two opposing axes; the ´classical axis´ mediated primarily by angiotensin II (Ang II), and the ´alternative axis´ mediated mainly by angiotensin(1-7) (Ang(1-7)). Ang(1-7) is a counter-regulatory mediator of Ang II, which also appears to be protective against cardiovascular disease. In addition, Ang(1-7) has been proposed to improve acute lung injury and fibrosis induced by endotoxin. However, its effect on multiple organ injury induced by sepsis remains unclear. Therefore, this study was to evaluate the Ang(1-7) effect on the development of multiple organ dysfunction in septic rats and to explore the possible mechanism. 
Materials and Methods: Cecal ligation and puncture (CLP) was performed to induce a polymicrobial sepsis peritonitis model in male Wistar rats. Subsequently, the animals were randomly assigned to receive an intravenous infusion of Ang(1-7) (1 mg/kg for 1 h) or an equivalent volume of vehicle (0.9% saline) solution at 3 and 6 h after surgical procedure. All hemodynamic and biochemical parameters were measured during the 24h observation. 
Results and Discussion: In septic rats, Ang(1-7) attenuated hypotension as well as the elevated serum level of blood urea nitrogen, creatinine and alanine aminotransferase. However, these improvements were not noted in CLP rats after single infusion of Ang(1-7) at 3 h alone. In addition, Ang(1-7) decrease serum IL-6 and liver caspase-3 expression induced by CLP. Superoxide levels in the lung  were also attenuated by Ang(1-7) in CLP rats. Moreover, Ang(1-7) administration was associated with significantly higher survival (82% vs. 38% at 24 h after CLP; P < 0.05).
Conclusion: Ang(1-7) prevented circulatory failure, alleviated multiple organ dysfunction, and decreased the mortality rate in septic rats receiving CLP. These beneficial effects of Ang(1-7) may be attributed to reducing IL-6 and caspase-3. Therefore, Ang(1-7) could be a potential therapeutic adjuvant in the early sepsis

Adjuvant potential of angiotensin-(1-7) in attenuating organ dysfunction in septic rats with peritonitis