Danser A H
Department of Pharmacology, Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam COEUR, The Netherlands.
Mol Cell Biochem. 1996;157(1-2):211-6. doi: 10.1007/BF00227900.
The existence of a local cardiovascular renin-angiotensin system (RAS) is often invoked to explain the long-term beneficial effects of RAS inhibitors in heart failure and hypertension. The implicit assumption is that all components of the RAS are synthesized in situ, so that local angiotensin II formation may occur independently of the circulating RAS. Evidence for this assumption however is lacking. The angiotensin release from isolated perfused rat hearts or hindlimbs depends on the presence of renal renin. When calculating the in vivo angiotensin production at tissue sites in humans and pigs, taking into account the extensive regional angiotensin clearance by infusing radiolabeled angiotensin I or II, it was found that angiotensin production correlated closely with plasma renin activity. Moreover, in pigs the cardiac tissue levels of renin and angiotensin were directly correlated with their respective plasma levels, and both in tissue and plasma the levels were undetectably low after nephrectomy. Similarly, rat vascular renin and angiotensin decrease to low or undetectable levels within 48 h after nephrectomy. Aortic renin has a longer half life than plasma renin, suggesting that renin may be bound by the vessel wall. In support of this assumption, both renin receptors and renin-binding proteins have been described. Like ACE, renin was enriched in a purified membrane fraction prepared from cardiac tissue. Binding of renin to cardiac vascular membranes may therefore be part of a mechanism by which renin is taken up from plasma. It appears that the concept of a local RAS needs to be reassessed. Local angiotensin formation in heart and vessel wall does occur, but depends, at least under normal circumstances, on the uptake of renal renin from the circulation. Tissues may regulate their local angiotensin concentrations by varying the number of renin receptors and/or renin-binding proteins, the ACE level, the amount of metabolizing enzymes and the angiotensin receptor density.
局部心血管肾素-血管紧张素系统（RAS）的存在常被用来解释RAS抑制剂在心力衰竭和高血压治疗中的长期有益作用。一个隐含的假设是，RAS的所有成分都是原位合成的，因此局部血管紧张素II的形成可能独立于循环RAS。然而，这一假设缺乏证据。从离体灌注的大鼠心脏或后肢释放的血管紧张素取决于肾素的存在。在计算人和猪组织部位的体内血管紧张素生成时，通过注入放射性标记的血管紧张素I或II来考虑广泛的局部血管紧张素清除情况，结果发现血管紧张素生成与血浆肾素活性密切相关。此外，在猪中，心脏组织中的肾素和血管紧张素水平与它们各自的血浆水平直接相关，肾切除术后组织和血浆中的水平均低至检测不到。同样，大鼠血管肾素和血管紧张素在肾切除术后48小时内降至低水平或检测不到的水平。主动脉肾素的半衰期比血浆肾素长，这表明肾素可能被血管壁结合。支持这一假设的是，已经描述了肾素受体和肾素结合蛋白。与ACE一样，肾素在从心脏组织制备的纯化膜组分中富集。因此，肾素与心脏血管膜的结合可能是肾素从血浆中摄取的一种机制的一部分。看来局部RAS的概念需要重新评估。心脏和血管壁中确实会发生局部血管紧张素的形成，但至少在正常情况下，这取决于从循环中摄取肾素。组织可以通过改变肾素受体和/或肾素结合蛋白的数量、ACE水平、代谢酶的量和血管紧张素受体密度来调节其局部血管紧张素浓度。
