Induction of renal artery hyperresponsiveness by alpha1-adrenoceptor in hepatorenal syndrome

// Xiaogang Zhang 1 , Xinsen Xu 1 , Yina Jiang 2 , Jianyu He 3 , Wenjing Wang 1 , Wei Li 1 , Xufeng Zhang 1 and Yi Lv 1 1 Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi’an 710061, China 2 Department of Pathology, First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi’an 710061, China 3 Department of Pharmacology, First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi’an 710061, China Correspondence to: Yi Lv, email: luyi169@126.com Keywords: hepatorenal syndrome; α1-adrenoceptor; hyperresponsiveness; renal artery; pathogenesis Received: February 17, 2017      Accepted: June 29, 2017      Published: November 25, 2017 ABSTRACT Objective: To investigate the potential role of alpha1-adrenoceptor (α1-AR) in the pathogenesis of hepatorenal syndrome. Methods: Hepatorenal syndrome was induced in male rats by intraperitoneal injection of D-galactosamine and orally treatment with α1-AR antagonist tamsulosin. Hyperresponsiveness of the renal artery contraction was evaluated by the laser-Doppler flowmetry and multimyograph system, while renal blood flow (cortical and medullary perfusion) was simultaneously measured. Renal artery ring segment tone was recorded with the myograph system, and concentration-response curves were obtained by cumulative administration of agonists. Results: This model developed acute renal and liver failure without renal damage in pathology, accompanied by significant hyperresponsiveness of renal artery contraction. After hepatorenal syndrome, plasma concentrations of tumor necrosis factor-α increased by two-fold, and α1-AR was significantly activated in the renal artery. Concentration-dependent vasoconstriction induced by noradrenaline was significantly decreased in the renal arteries of hepatorenal syndrome rat because of gradually decreased renal blood flow. Administration of tamsulosin prevented renal failure when given before the onset of liver injury, but it had no effect on liver injury by itself. Conclusion: α1-AR expression is positively associated with renal vasoconstriction induced by renal artery hyperresponsiveness in HRS. Therefore, α1-AR may be a potential target in the treatment of HRS.