Renal sodium-glucose cotransporter activity and aquaporin-2 expression in rat kidney during chronic nitric oxide synthase inhibition
Renal sodium-glucose cotransporter activity and aquaporin-2 expression in rat kidney during chronic nitric oxide synthase inhibition
复制标题
DOI：
10.1159/000109822
复制
发表时间：
2007-01-01
影响因子：
--
通讯作者：
Vidal, Norberto A.
中科院分区：
文献类型：
--
作者：
Borghese, Maria F. Albertoni;Majowicz, Monica P.;Vidal, Norberto A.
背景/目的：肾脏钠-葡萄糖共转运体(SGLT2)和水通道水通道蛋白-2(AQP2)在生理和病理条件下的肾小管钠水重吸收和细胞外液容量的调节中起重要作用。然而，有关SGLT2和AQP2在高血压中的表达和/或活性的研究很少，在慢性一氧化氮合酶(NOS)抑制所致的高血压过程中也没有报道。方法：用N-G-硝基-L-精氨酸甲酯(L-NAME)(20 mg/kg/24 h)灌胃6周(H6)或12周(H12)诱导大鼠高血压模型。用α-C-14-甲基葡萄糖主动摄取法测定SGLT2活性。免疫组织化学和/或免疫印迹法检测转运蛋白的表达水平。结果：H6和H12的SGLT2活性均降低；这既不是由于SGLT2表达的减少，也不是由于细胞膜磷脂组成的改变。H6组仅内侧延髓(IM)AQP2表达减弱，H12组外髓(OM)和IM AQP2表达均减弱。AQP2的表达减少可能是H12的尿量增加和尿渗透压降低的部分原因，因为我们在OM和IM中都获得了AQP2的表达与这些尿液参数之间的强烈相关性。结论：在一氧化氮合酶抑制诱导的大鼠高血压模型中，SGLT2活性和AQP2的表达被修饰以补偿动脉压的升高。然而，我们不能排除观察到的变化是由于NO产量本身减少的可能性。版权所有(C)2007 S.Karger AG，巴塞尔。
Background/Aims: The renal sodium glucose cotransporter (SGLT2) and the water channel aquaporin-2 (AQP2) play a critical role in tubular sodium and water reabsorption and in the regulation of extracellular fluid volume both in physiologic and pathophysiologic conditions. However, there is little information about SGLT2 and AQP2 expression and/or activity in hypertension and there are no reports during hypertension induced by chronic nitric oxide synthase (NOS) inhibition. Methods: Hypertension was induced in rats by oral administration of N-G-nitro-L-arginine methyl ester (L-NAME) (20 mg/kg/24 h) for 6 (H6) or 12 (H12) weeks. SGLT2 activity was measured using alpha-C-14-methylglucose active uptake. The expression level of transporters was assessed by immunohistochemistry and/or immunoblotting. Results: SGLT2 activity was reduced in both H6 and H12; this was due neither to a decrease in SGLT2 expression nor to a change in membrane phospholipid composition. In H6, AQP2 expression diminished only in the inner medulla (IM), while in H12 it diminished in both outer (OM) and IM. This reduced expression of AQP2 may partially account for the increased urinary volume and decreased urinary osmolality in H12, since we obtained a strong correlation between AQP2 expression and these urinary parameters in both OM and IM. Conclusion: We propose that in rats in which hypertension is induced by NOS inhibition, SGLT2 activity and AQP2 expression are modified to compensate for the elevated arterial pressure. However, we cannot discount the possibility that the observed changes are due to the decrease in NO production itself. Copyright (c) 2007 S. Karger AG, Basel.