Abstract
ObjectiveTo investigate the potential role of alpha1-adrenoceptor (α1-AR) in the pathogenesis of hepatorenal syndrome.MethodsHepatorenal 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.ResultsThis 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.Conclusionα1-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.
Highlights
Despite considerable advances in the treatment of end-stage liver disease, renal dysfunction remains common and contributes to the morbidity and mortality associated with hepatorenal syndrome (HRS) [1]
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
Summary
Despite considerable advances in the treatment of end-stage liver disease, renal dysfunction remains common and contributes to the morbidity and mortality associated with hepatorenal syndrome (HRS) [1]. It was reported that renal blood flow was reduced in patients with severe acute liver failure (ALF), indicating renal vasoconstriction and pathological change in those patients who develop. The pathogenesis of ALF-induced acute renal failure (ARF) and its underlying molecular mechanisms are poorly understood, several causal elements, such as splanchnic vasodilatation, reduction of effective arterial volume, and portal hypertension, have been considered as possible pathogenetic factors of renal injury [3, 4]. In HRS patients, splanchnic vasodilatation and decreased effective arterial volume antedate the development of renal failure, which activates a variety of compensatory mechanisms (the renin-angiotensin system, sympathetic nervous system, and increased release of antidiuretic hormone etc.), leading to the renal vasoconstriction [3, 5]. The decrease of renal blood flow in HRS may be due to the overexpressed renovascular response induced vasoconstriction
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
