Intracrine renin and angiotensin II: a novel role in cardiovascular and renal cellular regulation.
Intracrine renin and angiotensin II: a novel role in cardiovascular and renal cellular regulation.
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分泌内肾素和血管紧张素 II：在心血管和肾细胞调节中的新作用。
DOI：
10.1097/01.hjh.0000226188.90815.56
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发表时间：
2006
影响因子：
4.9
通讯作者：
Zhuo,JiaL
中科院分区：
文献类型：
--
作者：
Zhuo,JiaL
自世纪前Robert Tigerstedt发现肾素以来，对肾素-血管紧张素系统（RAS）的兴趣比以往任何时候都要强烈[1]。Tigerstedt将从家兔肾脏制备的生理盐水浸提液注射到其他家兔体内，观察到动脉血压显著升高，这导致了肾脏可能释放内分泌物质以控制全身血压的假设[1]。这种升压物质被Tigerstedt命名为renin。1934年，Harry Goldblatt证实并扩展了Tigerstedt在他关于两肾一夹肾性高血压的传奇性研究中发现的RAS [2]。几十年来，血管紧张素II被认为是一种内分泌肽，由肾源性肾素和肺源性血管紧张素转换酶（ACE）作用形成，并引起全身性高血压。RAS现在被公认为双重血管活性系统，既充当循环内分泌系统，又充当局部组织旁分泌/自分泌系统[3，4]。Re进一步将内分泌血管紧张素II定义为效应肽，其通过肾素、血管紧张素原和ACE的相互作用在细胞内合成或从细胞外血管紧张素II内化[5]。RAS级联的大多数或所有主要组分，包括血管紧张素原、肾素、ACE和血管紧张素II受体（AT 1或AT 2），已在心脏、肾上腺、脑和血管中得到证实[6，7]。肾素是级联反应中的限速酶，作用于肝细胞合成的底物血管紧张素原，形成血管紧张素I，血管紧张素I通过ACE转化为血管紧张素II。血管紧张素II进一步被氨肽酶代谢成活性片段血管紧张素III和/或血管紧张素IV。RAS级联反应的主要效应分子是血管紧张素II，尽管其他血管紧张素片段如血管紧张素III、血管紧张素1-7和血管紧张素IV已被证明具有生物活性[6]。许多组织中存在的肾素、血管紧张素原和ACE使得局部形成血管紧张素II成为可能，而血管紧张素II受体的表达对于血管紧张素II在靶位点诱导生物学效应是必不可少的。两种主要类型的血管紧张素II受体在心脏、肾脏、大脑、肾上腺和血管中表达，AT 1和AT 2 [6，7]。AT 1是G蛋白偶联受体，属于七种跨膜蛋白超家族。已在啮齿动物中鉴定出两种AT 1亚型，命名为AT 1A和AT 1B，但前者是肾脏、血管和心脏中的主要亚型[6]。虽然血管紧张素II的升压作用历来被认为是其主要作用，但它也刺激醛固酮合成，促进体内盐和液体潴留，并诱导心血管和肾组织中的细胞生长和增殖[4，6]。血管紧张素II的大多数已知作用是由AT 1受体介导的，AT 1受体与多种信号传导途径偶联，包括磷脂酶C、D和A2信号传导、促分裂原活化蛋白激酶和酪氨酸激酶。AT 1的激活导致磷酸肌醇水解、细胞内钙的动员和腺苷酸环化酶的抑制[6-8] AAS介导的作用的经典观点是细胞外血管紧张素II在质膜处结合其受体，并且受体的磷酸化激活下游信号传导并诱导细胞内反应[6]。然而，越来越多的证据表明，血管紧张素II与其膜AT 1受体的结合也启动了内吞（或内化）过程，促进效应物和受体进入细胞内区室的运输，在那里...
Since renin was discovered by Robert Tigerstedt more than a century ago, interest in the renin–angiotensin system (RAS) remains stronger than ever [1]. Tigerstedt injected saline extracts prepared from a rabbit kidney into other rabbits and observed marked increases in arterial blood pressure, which led to the hypothesis that the kidney might release an endocrine substance to control systemic blood pressure [1]. This pressor substance was named renin by Tigerstedt. It was Harry Goldblatt who confirmed and extended Tigerstedt’s discovery of the RAS in his legendary studies on two-kidney, one-clip renal hypertension in 1934 [2]. For several decades, angiotensin II was known as an endocrine peptide that is formed by the actions of kidney-derived renin and lungderived angiotensin-converting enzyme (ACE) and causes systemic hypertension. The RAS is now well recognized as a dual vasoactive system, acting as both a circulating endocrine system and a local tissue paracrine/autocrine system [3, 4]. Re further defined intracrine angiotensin II as the effector peptide that is either synthesized within a cell via interactions of renin, angiotensinogen and ACE or internalized from extracellular angiotensin II [5]. Most or all major components of the RAS cascade, including angiotensinogen, renin, ACE and angiotensin II receptors (AT1 or AT2), have been demonstrated in the heart, adrenal glands, brain and blood vessels [6, 7]. Renin, the rate-limiting enzyme in the cascade, acts on the hepatocyte-synthesized substrate angiotensinogen to form angiotensin I, which is converted to angiotensin II by ACE. Angiotensin II is further metabolized by aminopeptidases into the active fragments angiotensin III and/or angiotensin IV. The principal effector molecule of the RAS cascade is angiotensin II, although other angiotensin fragments such as angiotensin III, angiotensin 1–7 and angiotensin IV have been shown to be biologically active [6]. The presence of renin, angiotensinogen and ACE in many tissues makes local formation of angiotensin II possible, whereas expression of angiotensin II receptors is essential for angiotensin II to induce biological effects at target sites. Two major classes of angiotensin II receptors are expressed in the heart, kidney, brain, adrenals and blood vessels, AT1 and AT2 [6, 7]. AT1 is a G protein-coupled receptor belonging to the superfamily of seven transmembrane-spanning proteins. Two subtypes of AT1, designated AT1A and AT1B, have been identified in rodents, but the former is the predominant isoform in the kidney, blood vessels, and heart [6]. Although the pressor effect of angiotensin II is historically considered its primary action, it also stimulates aldosterone synthesis, promotes body salt and fluid retention, and induces cellular growth and proliferation in cardiovascular and renal tissues [4, 6]. Most of the known actions of angiotensin II are mediated by the AT1 receptor, which is coupled to multiple signaling pathways, including phospholipase C, D, and A2 signaling, mitogen-activated protein kinase, and tyrosine kinase. Activation of AT1 leads to phosphoinositide hydrolysis, mobilization of intracellular calcium, and inhibition of adenylate cyclase [6–8].The classic view of RAS-mediated actions is that extracellular angiotensin II binds its receptors at the plasma membrane, and phosphorylation of the receptor activates downstream signaling and induces intracellular responses [6]. Increasing evidence suggests, however, that binding of angiotensin II to its membrane AT1 receptors also initiates endocytotic (or internalization) processes that promote trafficking of both the effector and the receptor into intracellular compartments, where …
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影响因子：
--
作者：
Walter G. Thomas;Thomas J. Motel;C. Kule;Vijay Karoor;Kenneth M. Baker
通讯作者：
Walter G. Thomas;Thomas J. Motel;C. Kule;Vijay Karoor;Kenneth M. Baker
血管紧张素 II 刺激的培养血管平滑肌细胞中受体隔离与二酰甘油持续积累的相关性。
DOI：
--
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Griendling,KK;Delafontaine,P;Rittenhouse,SE;GimbroneJr,MA;Alexander,RW
通讯作者：
Alexander,RW
影响因子：
21.1
作者：
M. Gasparo;K. Catt;T. Inagami;J. Wright;T. Unger
通讯作者：
M. Gasparo;K. Catt;T. Inagami;J. Wright;T. Unger
肾素增加衰竭心脏中的内向钙电流。
DOI：
10.1097/01.hjh.0000226209.88312.db
发表时间：
2006
期刊：
Journal of hypertension.
影响因子：
--
作者：
DeMello,WalmorC
通讯作者：
DeMello,WalmorC
血管紧张素 II 1 型 (AT1) 受体介导的血管紧张素 II 在组织中的积累及其体内细胞内半衰期。
影响因子：
8.3
作者：
J. P. Kats;L. M. Lannoy;A. Danser;J. R. Meegen;P. Verdouw;M. Schalekamp
通讯作者：
M. Schalekamp