Siragy H M, Carey R M
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, 22908, USA.
J Clin Invest. 1996 Apr 15;97(8):1978-82. doi: 10.1172/JCI118630.
The renal effects of angiotensin II(AII) are attributed to AT1 receptors. In contrast, the function of renal AT2 receptors in unknown. Using a microdialysis technique, we monitored changes in renal interstitial fluid (RIF) prostaglandin E2 (PGE2) and cyclic guanosine 3', 5'-monophosphate (cGMP) in response to dietary sodium (Na) depletion alone, or Na depletion or normal Na diet combined with the AT1 receptor blocker, Losartan, the AT2 receptor blocker, PD 123319 (PD), or angiotensin II, individually or combined in conscious rats. Na depletion significantly increased PGE2 and cGMP. During Na depletion, Losartan decreased PGE2 and did not change cGMP. In contrast, PD significantly increased PGE2 and decreased cGMP. Combined administration of Losartan and PD decreased PGE2 and cGMP. During normal Na diet, RIF PGE2 and cGMP increased in response to angiotensin II. Neither Losartan nor PD, individually or combined, changed RIF PGE2 or cGMP. Combined administration of angiotensin II and Losartan or PD produced a significant decrease in response of PGE2 and cGMP to angiotensin II, respectively. These data demonstrate that activation of the reninangiotensin system during Na depletion increases renal interstitial PGE2 and cGMP. The AT1 receptor mediates renal production of PGE2. The AT2 receptor mediates cGMP. AT2 blockade potentiates angiotensin-induced PGE2 production at the AT1 receptor.
血管紧张素II（AII）的肾脏效应归因于AT1受体。相比之下，肾脏AT2受体的功能尚不清楚。我们采用微透析技术，监测清醒大鼠单独饮食性钠（Na）缺乏、或Na缺乏或正常Na饮食联合AT1受体阻滞剂氯沙坦、AT2受体阻滞剂PD 123319（PD）或血管紧张素II时肾间质液（RIF）中前列腺素E2（PGE2）和环磷酸鸟苷（cGMP）的变化。钠缺乏显著增加PGE2和cGMP。在钠缺乏期间，氯沙坦降低PGE2但不改变cGMP。相反，PD显著增加PGE2并降低cGMP。氯沙坦和PD联合给药降低PGE2和cGMP。在正常钠饮食期间，RIF中的PGE2和cGMP因血管紧张素II而增加。氯沙坦和PD单独或联合使用均未改变RIF中的PGE2或cGMP。血管紧张素II与氯沙坦或PD联合给药分别使PGE2和cGMP对血管紧张素II的反应显著降低。这些数据表明，钠缺乏期间肾素-血管紧张素系统的激活增加肾间质PGE2和cGMP。AT1受体介导肾脏PGE2的产生。AT2受体介导cGMP。AT2阻断增强血管紧张素在AT1受体处诱导的PGE2产生。
