Biochemistry and regulation of angiotensinogen.
Biochemistry and regulation of angiotensinogen.
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血管紧张素原的生物化学和调节。
DOI：
10.3109/10641968309048838
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Pierre Corvol
中科院分区：
文献类型：
--
作者：
Joël Ménard;Jacob Bouhnik;Eric Clauser;J. Richoux;Pierre Corvol
血管紧张素II和血管紧张素III是肾素-血管紧张素系统的活性肽，由酶促反应级联产生，其初始步骤是肾素与其底物血管紧张素原之间的反应。在血浆中，血管紧张素原的浓度是一个限制因素：酶促反应的Km在1和2 μ M之间，这取决于物种。因此，感兴趣的是测量其在血浆和组织中的水平，并检查可能影响其合成和释放的主要因素。血管紧张素原的完全纯化使得制备与血管紧张素原及其残余物（des-angio I-血管紧张素原）交叉反应的特异性抗体成为可能，并且目前用于放射免疫测定和免疫组织化学研究。少量的血管紧张素原储存在肝细胞中，可以通过免疫荧光检测和放射免疫测定。它也存在于近端肾小管细胞中，可能从肾小球滤液中重吸收，但肾小球细胞中不存在。几种激素能够增加肝脏血管紧张素原的合成及其释放。甲状腺素、血管紧张素II、地塞米松、炔雌醇和双肾切除术均增加合成和释放。肾上腺切除术和转化酶抑制伴随着血浆血管紧张素原的外周消耗增加，以及代谢和作用未知的去血管生成的I-血管紧张素原的蓄积。血管紧张素原在肾血流动力学中的主要作用通过其对离体灌注肾的作用来证明，这是一种与雌孕激素治疗的妇女的临床观察平行的实验观察，其肾血流量减少，即使在没有可检测到的血压升高的情况下。更好地了解各种物种中的肾素底物结构是设计血管紧张素原的抑制性类似物的必要条件，所述血管紧张素原的抑制性类似物将用于治疗高血压和水肿。
Angiotensin II and angiotensin III, the active peptides of the renin-angiotensin system, are produced by a cascade of enzymatic reactions, whose initial step is the reaction between renin and its substrate, angiotensinogen. In plasma, the concentration of angiotensinogen is a limiting factor: the Km of the enzymatic reaction is between 1 and 2 microM depending on the species. It is therefore of interest to measure its level in plasma and tissues and to examine the main factors which may influence its synthesis and release. The complete purification of angiotensinogen has made possible the preparation of specific antibodies which cross-react with both angiotensinogen and its residue, des-angio I-angiotensinogen, and are currently used in radioimmunoassays and immunohistochemical studies. A small amount of angiotensinogen is stored in hepatic cells, where it can be detected by immunofluorescence and measured by radioimmunoassay. It is also present in proximal tubular cells of the kidney, probably reabsorbed from glomerular filtrate, but it is absent from juxtaglomerular cells. Several hormones are able to increase liver synthesis of angiotensinogen and its release. Thyroxine, angiotensin II, dexamethasone, ethinyl-estradiol and binephrectomy increase both synthesis and release. Adrenalectomy and converting-enzyme inhibition are accompanied by an increased peripheral consumption of plasma angiotensinogen, and by accumulation of des-angio I-angiotensinogen whose metabolism and role are unknown. The major role of angiotensinogen in renal hemodynamics is demonstrated by its effects on the isolated perfused kidney, an experimental observation which parallels the clinical observation of women on estroprogestative therapy, whose renal blood flow is reduced, even in the absence of a detectable increase in their blood pressure. A better knowledge of renin substrate structure in various species is a necessary requirement for the design of inhibitory analogs of angiotensinogen which will have application for the treatment of hypertension and oedema.