Effects of alamandine on vascular and renal functions in lipopolysaccharide-induced sepsis model in rats

Sepsis is defined as uncontrolled inflammation leading to multiple organ system failure and dysfuncion. Acute kidney injury is an important cause of significant morbidity and mortality in sepsis. Alamandine (ALA) is a recently discovered endogenous peptide in the renin-angiotensin-aldosterone system and its effects on functional and vascular parameters in sepsis are unknown. In this study, ALA's effects, both as a pre-treatment and treatment agent in lipopolysaccharide (LPS)-induced rat sepsis model were investigated. Its effects on systemic and renal dysfunction were studied via functional, hemodynamic, vascular, molecular, biochemical and histopathological evaluations. 10 milligrams/kilogram intraperitoneal LPS injection in Sprague-Dawley rats led to liver and renal injury, reduced blood flow in several organ systems, and renal dysfunction in 20 hours. Results showed that ALA, as a treatment agent, could alleviate systemic and renal inflammation, prevent the increase of mortality, ameliorate the vascular dysfunction and the decrease of blood flow, decrease the renal inducible nitric oxide (iNOS) and caspase gene expression levels, and reduce the renal and hepatic injury. ALA was effective as a treatment agent on LPS-induced changes in the renal arterial bed. In addition, ALA-related receptor gene expressions showed differences with LPS in the kidney and ALA treatment reversed these. These results show that ALA exerts corrective effects on acute kidney injury and systemic changes in a sepsis model in rats, through reducing increased iNOS gene expression and anti-inflammatory, anti-pyroptotic, and anti-apoptotic effects on hemodynamic and vascular functions.