Vasopressin regulates the renin-angiotensin-aldosterone system via V1a receptors in macula densa cells
Vasopressin regulates the renin-angiotensin-aldosterone system via V1a receptors in macula densa cells
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DOI：
10.1152/ajprenal.00088.2008
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发表时间：
2008-07-01
影响因子：
4.2
通讯作者：
Tanoue, Akito
中科院分区：
文献类型：
--
作者：
Aoyagi, Toshinori;Izumi, Yuichiro;Tanoue, Akito
神经肽类激素精氨酸加压素(AVP)通过血管加压素V2受体(V2R)发挥抗利尿作用，而血管加压素V1a受体(V1aR)在肾脏中的作用尚不清楚。此前，我们报告了V1a受体缺陷(V1aR(-/-))小鼠的血浆容量和血压下降(Koshimizu T，Nasa Y，Tanoue A，Oikawa R，Kawahara Y，Kiyono Y，Adachi T，Tanaka T，Kukki T，Mori T.proc Natl Acad Sci USA 103：7807-7812,2006)。在这项研究中，我们利用V1aR(-/-)小鼠研究了V1aR对尿液浓度、肾功能和肾素-血管紧张素系统(RAS)的作用。V1aR(-/-)小鼠的尿量大于野生型小鼠，尤其是水负荷时，肾小球滤过率(GFR)、尿钠排泄、肾脏AVP依赖的cAMP生成、V2R和水通道蛋白2(AQP2)的表达降低，表明GFR和V2R-AQP2系统的减少导致V1aR(-/-)小鼠的尿液浓度降低。由于GFR和V2R-AQP2系统受RAS的调节，我们分析了V1aR(-/-)小鼠的肾素和血管紧张素II，发现血浆肾素和血管紧张素II降低。V1aR(-/-)小鼠颗粒细胞肾素表达减少，导致血浆肾素水平下降。此外，在V1aR(-/-)小鼠中，V1aR特异表达的致密斑(MD)细胞中肾素刺激因子如神经元型一氧化氮合酶和环氧合酶-2的表达减少。这些数据表明，AVP通过激活RAS和随后的V2R-AQP2系统来调节MD细胞中的V1aR，从而调节体液平衡和GFR。
The neuropeptide hormone argininevasopressin (AVP) is well known to exert its antidiuretic effect via the vasopressin V2 receptor (V2R), whereas the role of the vasopressin V1a receptor (V1aR) in the kidney remains to be clarified. Previously, we reported decreased plasma volume and blood pressure in V1a receptor-deficient (V1aR(-/-)) mice (Koshimizu T, Nasa Y, Tanoue A, Oikawa R, Kawahara Y, Kiyono Y, Adachi T, Tanaka T, Kuwaki T, Mori T. Proc Natl Acad Sci USA 103: 7807 - 7812, 2006). In this study, we investigated the role of V1aR in urine concentration, renal function, and the renin- angiotensin system (RAS) using V1aR(-/-) mice. Urine volume of V1aR(-/-) mice was greater than that of wild- type mice, particularly when water was loaded, while the glomerular filtration rate (GFR), urinary NaCl excretion, AVP- dependent cAMP generation, V2R, and aquaporin 2 (AQP2) expression in the kidney were lower, indicating that the diminished GFR and V2R- AQP2 system led to impaired urinary concentration in V1aR(-/-) mice. Since the GFR and V2R- AQP2 system are regulated by RAS, we analyzed renin and angiotensin II in V1aR(-/-) mice and found that the plasma renin and angiotensin II were decreased. The expression of renin in granule cells was decreased in V1aR(-/-) mice, which led to a decreased level of plasma renin. In addition, the expression of renin stimulators such as neuronal nitric oxide synthase and cyclooxygenase-2 in macula densa (MD) cells, where V1aR was specifically expressed, was decreased in V1aR(-/-) mice. These data indicate that AVP regulates body fluid homeostasis and GFR via the V1aR in MD cells by activating RAS and subsequently the V2R-AQP2 system.