Angiotensin 1-7 in an experimental septic shock model

Area of Science:

• Physiology
• Pharmacology
• Critical Care Medicine

Background:

• The renin-angiotensin system is implicated in septic shock pathophysiology.
• Angiotensin 1-7 (Ang-(1-7)), an anti-inflammatory peptide, may offer therapeutic benefits.

Purpose of the Study:

• To investigate the effects of Ang-(1-7) infusion on the development and severity of septic shock.
• To evaluate Ang-(1-7) as a potential treatment for sepsis.

Main Methods:

• A randomized, controlled study in 14 anesthetized, ventilated sheep with induced bacterial peritonitis.
• Intravenous infusion of Ang-(1-7) or placebo immediately after sepsis induction.
• Standardized fluid resuscitation, antimicrobial therapy, and peritoneal lavage initiated 4 hours post-sepsis.

Main Results:

• Septic shock was prevented in 6/7 sheep receiving Ang-(1-7).
• Significantly lower norepinephrine requirements (0.4 vs 4.3 μg/kg/min) were observed in the Ang-(1-7) group.
• Reduced plasma interleukin-6 and creatinine levels, alongside improved platelet count and PaO2/FiO2 ratio, were noted with Ang-(1-7) treatment.

Conclusions:

• Early Ang-(1-7) infusion effectively prevented septic shock in an experimental model.
• Ang-(1-7) reduced the need for vasopressors and mitigated key indicators of organ dysfunction.
• This study highlights Ang-(1-7) as a potential therapeutic agent for septic shock.