Angiotensin-(1-7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb
Angiotensin-(1-7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb
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DOI：
10.14814/phy2.14015
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发表时间：
2019-03-01
影响因子：
2.5
通讯作者：
Juncos, Luis, I
中科院分区：
文献类型：
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作者：
Dibo, Paula;Maranon, Rodrigo O.;Juncos, Luis, I
钠在Henle厚升环（TAL）中的转运受到多种因素的严格调控，尤其是肾素-血管紧张素系统（RAS）的关键终产物血管紧张素II （Ang II）。然而，RAS的另一种最终产物血管紧张素-(1-7)[Ang-(1-7)]可能会抵消Ang II的一些作用。事实上，它通过其在近端和远端小管的作用引起血管舒张和促进尿钠。然而，它对TAL的影响尚不清楚。由于TAL表达Mas受体，一种Ang-(1-7)配体，反过来可以增加NO并抑制Na+转运，我们假设Ang-(1-7)通过Mas受体/NO依赖机制抑制TAL中的Na转运。我们通过测量TAL悬浮液中依赖运输的耗氧量（VO2）来验证这一点。给药Ang-(1-7)降低VO2；二甲基阿米洛利和速尿阻止了这一作用，表明Ang-(1-7)抑制TAL中转运依赖性的VO2。Ang-(1-7)也增加了一氧化氮水平，一氧化氮是TAL中Na+运输的已知抑制剂。Mas受体拮抗剂D-Ala改善了Ang-(1-7)对VO2和NO水平的影响，这实际上表明Ang-(1-7)可能通过Mas受体依赖性的NO通路激活来抑制TAL中转运依赖性的VO2。事实上，用L-NAME阻断NO合成可以阻止Ang-(1-7)对VO2的抑制作用。我们的数据表明，Ang-(1-7)可能通过Mas受体依赖性的NO增加来调节TAL Na+的运输，从而抑制运输活性。
Sodium transport in the thick ascending loop of Henle (TAL) is tightly regulated by numerous factors, especially angiotensin II (Ang II), a key end-product of the renin-angiotensin system (RAS). However, an alternative end-product of the RAS, angiotensin-(1-7) [Ang-(1-7)], may counter some of the Ang II actions. Indeed, it causes vasodilation and promotes natriuresis through its effects in the proximal and distal tubule. However, its effects on the TAL are unknown. Because the TAL expresses the Mas receptor, an Ang-(1-7) ligand, which in turn may increase NO and inhibit Na+ transport, we hypothesized that Ang-(1-7) inhibits Na transport in the TAL, via a Mas receptor/NO-dependent mechanism. We tested this by measuring transport-dependent oxygen consumption (VO2) in TAL suspensions. Administering Ang-(1-7) decreased VO2; an effect prevented by dimethyl amiloride and furosemide, signifying that Ang-(1-7) inhibits transport-dependent VO2 in TAL. Ang-(1-7) also increased NO levels, known inhibitors of Na+ transport in the TAL. The effects of Ang-(1-7) on VO2, as well as on NO levels, were ameliorated by the Mas receptor antagonist, D-Ala, in effect suggesting that Ang-(1-7) may inhibit transport-dependent VO2 in TAL via Mas receptor-dependent activation of the NO pathway. Indeed, blocking NO synthesis with L-NAME prevented the inhibitory actions of Ang-(1-7) on VO2. Our data suggest that Ang-(1-7) may modulate TAL Na+ transport via Mas receptor-dependent increases in NO leading to the inhibition of transport activity.