Mechanism of the protective effect of α_1A-AR antagonist on renal ischemic injury in rats with hepatorenal syndrome

Objective: To study the mechanism of the protective effect of α_1A-AR antagonist Tamsulosin (Tam) on renal ischemic injury in hepatorenal syndrome (HRS) rats. Methods: HRS was induced in male Sprague-Dawley (SD) rats by intraperitoneal injection of D-(+)-galactosamine hydrochloride (GalN). Thirty-two HRS rats were divided into 3 groups randomly. Then surgical occlusions of the infrahepatic inferior vena cave (OIVC) were performed; Tam, an α_1A-AR antagonist, was administered daily before injection of GalN. During the operation, hemodynamic changes of the kidney and liver were measured by laser Doppler flowmetry (LDF). Serum samples were collected to measure serum levels of liver and renal function. At the same time, renal and liver samples were harvested and stained by HE and immunohistochemistry. Other parts of the sample were fixed with 2.5% glutaral to observe the cellular ultrastructure of renal and vascular endothelium by electron microscope. Results: OIVC developed much severe ischemic injury in the kidney and liver of HRS rats. The renal cortex blood perfusion (RCBP) of HRS rats decreased rapidly after OIVC, and did not return to baseline after reflow. Pathological study showed severe injury of the liver and kidney. However, expressions of alpha-1 AR on renal artery and kidney were reduced in those rats that had received Tam before OIVC. Histological examination of the kidney also showed few abnormalities. Conclusion: Marked increases of contractive response of renal artery of HRS rats induced by up-regulation of α₁-AR may be associated with a high risk of progression to acute renal failure in HRS rats after ischemia. Tamsulosin has a protective effect on renal ischemic injury through reducing α_1A-AR overexpression in HRS rats.