Danser A H, Schalekamp M A
Cardiovasculair Onderzoeksinstituut Erasmus, Universiteit Rotterdam (COEUR), The Netherlands.
Heart. 1996 Nov;76(3 Suppl 3):28-32. doi: 10.1136/hrt.76.3_suppl_3.28.
The beneficial effects of angiotensin converting enzyme (ACE) inhibitors in heart failure appear to be independent, at least in part, of their effect on blood pressure. The existence of a local cardiac renin angiotensin system is often suggested as an explanation. It has been known for some time that a substantial proportion of arterially delivered angiotensin I is converted to angiotensin II by ACE of the coronary vascular endothelium. The levels of angiotensin II in cardiac tissue are several times the levels of angiotensin II in circulating blood. Recent evidence suggests that most of the angiotensin II in the heart is not derived from angiotensin I in the circulation, and that most of the angiotensin I in cardiac tissue is generated in the tissue itself. On the other hand, renin mRNA levels are very low or undetectable in the normal heart. In addition, studies on the effects of bilateral nephrectomy on the cardiac tissue levels of renin, angiotensin I, and angiotensin II in pigs have indicated that cardiac renin originates from the kidney and that cardiac generation of angiotensin I and angiotensin II depends on renin from the kidney. Intracardiac synthesis of renin may occur under pathological conditions and during fetal development. The fact that angiotensins are generated by the heart raises the possibility of local mechanisms to regulate the concentrations of these peptides at certain tissue sites. For example, preliminary evidence suggests that binding of renin to cardiac membranes is a mechanism by which renin is taken up by the heart. A specific renin binding protein has been identified in cardiac tissue. Cardiac ACE levels may also influence local angiotensin II formation and are, in part, determined by the so called insertion/deletion ACE gene polymorphism. More detailed knowledge on the site of angiotensin generation and on its regulation will improve our understanding of the role of the renin-angiotensin system in cardiac function, hypertrophy, and postinfarction remodelling.
血管紧张素转换酶（ACE）抑制剂对心力衰竭的有益作用似乎至少部分独立于其对血压的影响。人们常常认为存在局部心脏肾素血管紧张素系统可以解释这一现象。一段时间以来，人们已经知道，动脉输送的血管紧张素I有很大一部分被冠状血管内皮的ACE转化为血管紧张素II。心脏组织中血管紧张素II的水平是循环血液中血管紧张素II水平的几倍。最近的证据表明，心脏中的大多数血管紧张素II并非来自循环中的血管紧张素I，而且心脏组织中的大多数血管紧张素I是在组织自身中产生的。另一方面，正常心脏中肾素mRNA水平非常低或无法检测到。此外，对猪进行双侧肾切除对心脏组织中肾素、血管紧张素I和血管紧张素II水平影响的研究表明，心脏肾素起源于肾脏，心脏中血管紧张素I和血管紧张素II的产生依赖于来自肾脏的肾素。在病理条件下和胎儿发育期间可能会发生心脏内肾素的合成。心脏产生血管紧张素这一事实增加了在某些组织部位调节这些肽浓度的局部机制的可能性。例如，初步证据表明肾素与心脏膜的结合是心脏摄取肾素的一种机制。在心脏组织中已鉴定出一种特定的肾素结合蛋白。心脏ACE水平也可能影响局部血管紧张素II的形成，并且部分由所谓的插入/缺失ACE基因多态性决定。对血管紧张素产生部位及其调节的更详细了解将提高我们对肾素 - 血管紧张素系统在心脏功能、肥大和心肌梗死后重塑中作用的理解。
