Jonassen T E, Nielsen S, Christensen S, Petersen J S
Department of Pharmacology, the Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
Am J Physiol. 1998 Aug;275(2):F216-25. doi: 10.1152/ajprenal.1998.275.2.F216.
Experiments were performed to investigate vasopressin type 2 receptor (V2)-mediated renal water reabsorption and the renal expression of the vasopressin-regulated water channel aquaporin-2 (AQP-2) in cirrhotic rats with sodium retention but without ascites. In addition, the expression of the furosemide-sensitive type 1 Na-K-2Cl cotransporter (BSC-1) and the natriuretic response to an intravenous test dose furosemide (7.5 mg/kg) during acute V2-receptor blockade was measured. Acute V2-receptor blockade with the selective nonpeptide antagonist OPC-31260 (800 microg . kg-1 . h-1) was performed during conditions in which volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 150 mM glucose. OPC-31260 produced a significantly smaller increase in urine flow rate (-26%) and free water clearance (-18%) in cirrhotic rats than in control rats. The natriuretic response to an intravenous test dose furosemide (7.5 mg/kg) was significantly increased in cirrhotic rats (+52%), but pretreatment with OPC-31260 did not affect the natriuretic response to furosemide in neither cirrhotic nor in control rats. Semiquantitative immunoblotting showed a significant downregulation of AQP-2 in the renal cortex (-72%) and in the outer medulla (-44%). The relative expression of BSC-1 in the outer medulla was unchanged in cirrhotic rats. The corticopapillary gradient of Na was significantly increased in cirrhotic rats. Since daily urine flow rate was similar in cirrhotic and sham-operated rats, we suggest that non-vasopressin-mediated water reabsorption is increased in cirrhotic rats probably as a result of an increased corticomedullary gradient due to exaggerated NaCl reabsorption in the thick ascending limb of Henle's loop.
进行实验以研究2型血管加压素受体（V2）介导的肾水重吸收以及血管加压素调节的水通道蛋白2（AQP-2）在无腹水但有钠潴留的肝硬化大鼠中的肾表达。此外，还测量了速尿敏感的1型钠-钾-2氯共转运体（BSC-1）的表达以及急性V2受体阻断期间静脉注射速尿试验剂量（7.5mg/kg）的利钠反应。在通过计算机驱动、伺服控制静脉输注150mM葡萄糖防止容量耗竭的条件下，用选择性非肽拮抗剂OPC-31260（800μg·kg-1·h-1）进行急性V2受体阻断。与对照大鼠相比，OPC-31260使肝硬化大鼠的尿流率（-26%）和自由水清除率（-18%）的增加显著更小。肝硬化大鼠对静脉注射速尿试验剂量（7.5mg/kg）的利钠反应显著增加（+52%），但用OPC-31260预处理对肝硬化大鼠和对照大鼠的速尿利钠反应均无影响。半定量免疫印迹显示肾皮质（-72%）和外髓质（-44%）中AQP-2显著下调。肝硬化大鼠外髓质中BSC-1的相对表达未改变。肝硬化大鼠中钠的皮质乳头梯度显著增加。由于肝硬化大鼠和假手术大鼠的每日尿流率相似，我们认为肝硬化大鼠中非血管加压素介导的水重吸收增加可能是由于亨利袢升支粗段氯化钠重吸收增加导致皮质髓质梯度增加的结果。
