Role of angiotensin AT(2) receptors in natriuresis: Intrarenal mechanisms and therapeutic potential.
Role of angiotensin AT(2) receptors in natriuresis: Intrarenal mechanisms and therapeutic potential.
复制标题
DOI：
10.1111/1440-1681.12059
复制
发表时间：
2013-08
影响因子：
2.9
通讯作者：
Padia SH
中科院分区：
文献类型：
--
作者：
Carey RM;Padia SH
肾素-血管紧张素系统是一个协调的激素级联，对血压（BP）和肾功能的调节至关重要。血管紧张素II （Ang II）是主要的血管紧张素效应肽，与两种主要受体结合，1型（AT1Rs）和2型（AT2Rs）。AT1Rs产生抗尿钠和升高血压，而AT2Rs则相反，诱导尿钠和降低血压。AT2Rs在成人肾脏，尤其是近端肾小管中高度表达。在at2r缺失的小鼠中，与野生型动物相比，长期输注Ang II会导致升压和抗尿钠过敏反应。at2r介导的利钠反应的主要内源性受体配体似乎是去天冬氨酸1-Ang II （Ang III）而不是Ang II。最近的研究表明，Ang II需要通过氨肽酶A代谢到Ang III以诱导尿钠，抑制氨肽酶N可增加肾内Ang III并增强Ang III诱导的尿钠。肾多巴胺能系统是另一个重要的利钠途径。肾近端小管d1样受体（D1LIKERs）控制约50%的基础钠（Na+）排泄。我们最近发现，近端小管D1LIKERs诱导的钠尿需要激活AT2R，并且D1LIKER刺激通过循环amp依赖机制诱导AT2Rs向根尖质膜募集。使用强效AT2R非肽激动剂化合物21的初步研究表明，在存在和不存在AT1R阻断的情况下，钠尿都存在，这表明该化合物在液体潴留状态和高血压中的治疗潜力。
The renin-angiotensin system is a coordinated hormonal cascade critical for the regulation of blood pressure (BP) and kidney function. Angiotensin II (Ang II), the major angiotensin effector peptide, binds to two major receptors, type-1 (AT1Rs) and type-2 (AT2Rs). AT1Rs engender antinatriuresis and raise BP, whereas AT2Rs oppose these effects, inducing natriuresis and reducing BP AT2Rs are highly expressed in the adult kidney, especially in the proximal tubule. In AT2R-null mice, long-term Ang II infusion results in pressor and antinatriuretic hypersensivivity compared to responses in wild-type animals. The major endogenous receptor ligand for AT2R-mediated natriuretic responses appears to be des-aspartyl1-Ang II (Ang III) instead of Ang II. Recent studies have demonstrated that Ang II requires metabolism to Ang III by aminopeptidase A in order to induce natriuresis and that inhibition of aminopeptidase N increases intrarenal Ang III and augments Ang III-induced natriuresis. The renal dopaminergic system is another important natriuretic pathway. Renal proximal tubule D1-like receptors (D1LIKERs) control approximately 50% of basal sodium (Na+) excretion. We have recently found that natriuresis induced by proximal tubule D1LIKERs requires AT2R activation and that D1LIKER stimulation induces recruitment of AT2Rs to the apical plasma membrane via a cyclic AMP-dependent mechanism. Initial studies employing potent AT2R non-peptide agonist Compound 21 demonstrate natriuresis in both the presence and absence of AT1R blockade indicating the therapeutic potential of this compound in fluid retaining states and hypertension.
登录
查看更多内容
影响因子：
8.3
作者：
Carey, RM
通讯作者：
Carey, RM
DOI：
10.1152/ajprenal.00092.2005
发表时间：
2006-02-01
影响因子：
4.2
作者：
Hakam, AC;Siddiqui, AH;Hussain, T
通讯作者：
Hussain, T
影响因子：
8.3
作者：
Hakam, AC;Hussain, T
通讯作者：
Hussain, T
影响因子：
4.8
作者：
Herrera, Marcela;Garvin, Jeffrey L.
通讯作者：
Garvin, Jeffrey L.
影响因子：
8.3
作者：
Carey, RM
通讯作者：
Carey, RM