Histological and Immunohistochemical Basis of the Effect of Aminoguanidine on Renal Changes Associated with Hemorrhagic Shock in a Rat Model

Acute kidney failure is the main cause of death among patients with severe trauma due to massive blood loss and hemorrhagic shock (HS). Renal cell injury is caused by tissue ischemia. Renal ischemia initiates a complex and interconnected chain of events resulting in cell injury and renal cell necrosis. Nitric oxide plays a crucial role in renal function and can be inhibited by aminoguanidine (AG). We studied whether AG can ameliorate pathological renal changes associated with HS syndrome in a rat model and explored the AG protection mechanism. Rats were intraperitoneally injected with heparin sodium and mean arterial blood pressure was monitored. Animals were divided into three groups: control (without hemorrhage), with or without intra-arterially injected AG; HS (blood continuously withdrawn or reinfused to maintain an MABP of 35-40 mmHg); and HS with AG. We found that AG decreased plasma concentrations of urea, creatinine, and nitrates; ameliorated histological changes of HS-induced rats; and decreased the expressions of inducible nitrogen oxide synthase (iNOS), proapoptotic protein (BAX), and vitamin D receptors (VDR). AG ameliorated kidney injury by inhibiting iNOS resulting in decreased BAX and VDR expressions. Therefore, a therapeutic strategy targeting AG may provide new insights into kidney injury during severe shock.