Extrarenal renin and blood pressure regulation. An alternative viewpoint.
Extrarenal renin and blood pressure regulation. An alternative viewpoint.
复制标题
肾外肾素和血压调节。
DOI：
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发表时间：
1989
影响因子：
3.2
通讯作者：
D. Campbell
中科院分区：
文献类型：
--
作者：
D. Campbell
越来越多的证据表明，血管紧张素 I 和 II 的主要产生部位是外周组织。考虑到血管紧张素 I 广泛转化为血管紧张素 II 以及两种肽在外周组织中的清除，血管紧张素 I 和 II 在静脉血中的含量都太高，无法仅用它们在血液中的产生来解释。许多间接证据支持组织中血管紧张素产生的这一论点，并表明血管紧张素的组织产生在血压调节中发挥重要作用。组织肾素可能代表血浆的摄取和/或局部合成，但尽管可以轻松地在组织中测量肾素样活性，但由于非肾素酶的干扰和无活性肾素的无意激活，其解释是有问题的。此外，考虑到除肾素以外的酶能够从血管紧张素原中释放血管紧张素I和血管紧张素II，因此肾素在组织中血管紧张素的产生中没有必然的作用。由于组织产生是血浆血管紧张素的主要来源，双侧肾切除术后血浆血管紧张素水平下降表明肾源性肾素是组织血管紧张素产生的主要贡献者。这一论点得到了证据的支持，即血管肾素样活性是肾源性的，并且在血管紧张素依赖性升压机制中起主导作用。无肾病受试者血浆中无活性肾素的接近正常水平表明无活性肾素的肾外合成，并且已在各种非肾组织中鉴定出肾素mRNA。目前正在研究这些组织是否也能够将非活性肾素加工成活性肾素，及其在局部血管紧张素产生和血压调节中的作用。
There is increasing evidence that a major site of production of angiotensin I and II is peripheral tissue. Both angiotensin I and II are present in venous blood in amounts far too high to be explained by their generation in blood alone, given the extensive conversion of angiotensin I to angiotensin II and clearance of both peptides across peripheral tissues. Much indirect evidence supports this argument for angiotensin production in tissues, and indicates that tissue production of angiotensin plays an important role in regulation of blood pressure. Tissue renin may represent uptake from plasma and/or local synthesis, but despite the ease with which renin-like activity can be measured in tissues, its interpretation is problematic because of interference by nonrenin enzymes and inadvertent activation of inactive renin. Moreover, given that enzymes other than renin are able to liberate angiotensin I and angiotensin II from angiotensinogen, there is no obligatory role for renin in angiotensin production in tissues. Inasmuch as tissue production is the major source of plasma angiotensin, the fall in plasma angiotensin levels after bilateral nephrectomy indicates that kidney-derived renin is the major contributor to tissue angiotensin production. This argument is supported by evidence that vascular renin-like activity is kidney-derived, and plays a dominant role in angiotensin-dependent pressor mechanisms. Near-normal levels of inactive renin in plasma of anephric subjects indicates extrarenal synthesis of inactive renin, and renin mRNA has been identified in various nonrenal tissues. Whether these tissues are also able to process inactive renin to active renin, and its role in local angiotensin production and blood pressure regulation, are currently being investigated.