RAS Equilibrium Involves in Mesenteric Lymph Return-Mediated Acute Kidney Injury in Mice Underwent Acute Hemorrhage

Background: Previous studies demonstrated renin-angiotensin system (RAS) played vital roles in shock-induced organ injury, and mesenteric lymph return was involved in hemorrhagic shock-induced acute kidney injury (AKI). Nevertheless, whether RAS is involved in PHSML-mediated AKI remains unclear. Therefore, this study investigated the role of RAS in post-hemorrhagic shock mesenteric lymph (PHSML)-induced AKI. Methods: After acute hemorrhage and fluid resuscitation, the mice were treated with mesenteric lymph duct ligation (MLDL) and administrations of angiotensin converting enzyme (ACE) inhibitor enalapril, angiotensin (1-7) (Ang (1-7)), angiotensin II (Ang II) type 1 receptor (AT1R) inhibitor losartan, respectively. In addition, the parts of mice with hemorrhage plus MLDL were treated with Ang II, Mas receptor (MasR) inhibitor A-779, respectively. Meanwhile, the ACE2-/- mice received hemorrhage plus MLDL. At 4 h after resuscitation, the kidneys were harvested for the observation of histomorphology and measurement of ACE, ACE2, AT1R, MasR expressions and Ang II and Ang (1-7) levels.Results: Hemorrhagic shock induced renal tissue injury, increased the ACE and AT1R expressions, decreased the ACE2 and MasR expressions in kidney, accompanied by elevated Ang II and depressed Ang (1-7) in kidney. These adverse effects were partially reversed by MLDL or administrations of enalapril, Ang-(1-7), and losartan, respectively. In addition, the beneficial role of MLDL was reversed by ACE2 deficiency and Ang II or A-779 administrations. Conclusion: MLDL alleviates hemorrhagic shock-induced AKI in mice is related to the equilibrium ACE-AngII-AT1R and ACE2-Ang (1-7)-MasR axis.