Angiotensin aldosterone inhibitors improve survival and ameliorate kidney injury induced by sepsis through suppression of inflammation and apoptosis

Sepsis is an extensive life-threatening illness that occurs due to an abnormal host response that extends through the initial storm of inflammation and oxidative stress and terminates at the late stage of immunosuppression. Among global intensive care units, sepsis-induced acute kidney injury is reported with high mortality rate. The purpose of this study was to evaluate the protective effect of the renin angiotensin aldosterone system (RAAS) inhibition on sepsis outcomes. Cecal ligation and puncture (CLP) procedure was applied for sepsis induction. The experimental design constituted of five groups of rats: sham, CLP-nontreated and CLP-treated with ramipril (10 mg/kg, p.o.), losartan (20 mg/kg, i.p.) and spironolactone (25 mg/kg, p.o.). Twenty-four hours after surgery, rats were euthanized for blood and tissue samples, which were used for assessment of serum inflammatory markers, and oxidative stress parameters, as well as to kidney function parameters. The tissue samples were used for histological and caspase-3 assessment. A survival study was conducted using another set of animals. Our results showed that the different RAAS inhibitors showed protective effects evidenced by enhanced overall survival following sepsis (80% in ramipril and spironolactone-treated and 60% in losartan-treated vs. 10% in the septic group), in addition to improved renal function parameters and reduction of oxidative stress and inflammation. The timely use of RAAS inhibitors during sepsis might represent a new therapeutic approach in septic patient.