Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, A210-753 McDermot Avenue, Winnipeg, MB R3E 0W3, Canada.
Can J Physiol Pharmacol. 2010 Nov;88(11):1115-21. doi: 10.1139/y10-090.
The hepatorenal reflex, activated by intrahepatic adenosine, is involved in the regulation of urine production in healthy rats and renal pathogenesis secondary to liver injury. Hepatic adenosine A1 receptors regulate the hepatorenal reflex. The aim of the present study was to evaluate whether caffeine mediates renal natriuresis and diuresis in healthy and diseased liver through this mechanism. Rats were anesthetized and instrumented to monitor systemic, hepatic, and renal circulation and urine production. Intrahepatic (intraportal but not intravenous) caffeine (5 mg·kg-1) increased urine flow (82%) in healthy rats. This effect was abolished by liver denervation. Intraportal infusion of adenosine decreased urine production, and this response was abolished by intraportal but not intravenous caffeine. Liver injury was induced by intraperitoneal injection of thioacetamide (500 mg·kg-1), and functional assessment was performed 24 h later. Liver injury was associated with lower (30%) glomerular filtration rate, lower (~18%) renal arterial blood flow, and lower urine production. Intraportal but not intravenous caffeine improved basal urine production and renal ability to increase urine production in response to saline overload. The liver-dependent diuretic effect of caffeine is consistent with the hypothesis for the adenosine-mediated mechanism of hepatorenal syndrome.
肝肾功能反射，由肝内腺苷激活，参与健康大鼠尿液生成的调节和肝损伤继发的肾脏发病机制。肝腺苷 A1 受体调节肝肾功能反射。本研究旨在评估咖啡因是否通过这种机制介导健康和患病肝脏的肾脏利钠和利尿作用。大鼠麻醉并进行仪器监测以监测全身、肝和肾循环以及尿液生成。肝内（门静脉内而非静脉内）给予咖啡因（5mg·kg-1）可使健康大鼠的尿量增加（约 82%）。肝去神经支配可消除这种作用。门静脉内给予腺苷可减少尿量，而这种反应可被门静脉内而非静脉内给予的咖啡因消除。通过腹腔内注射硫代乙酰胺（500mg·kg-1）诱导肝损伤，并在 24 小时后进行功能评估。肝损伤与肾小球滤过率降低（约 30%）、肾动脉血流减少（约 18%）和尿量减少有关。门静脉内而非静脉内给予咖啡因可改善基础尿量和肾脏对盐水超负荷的尿液生成增加的能力。咖啡因的肝依赖性利尿作用与腺苷介导的肝肾综合征机制的假设一致。
