<International Circulation>: Your presentation today was on the implications of the local cardiac RAS. Could you briefly explain that for us?

　　《国际循环》：您今天的演讲是关于心脏局部RAAS的作用。能否简单介绍一下您演讲的内容？
　　Dr Ferro: Essentially， I was talking about the importance of the local renin-angiotensin system (RAS) in the heart. It is well known that the circulating renin-angiotensin system is important in regulating cardiovascular function. It is a target for drugs (ACE inhibitors and angiotensin receptor blockers) and we know that the ACE inhibitors and angiotensin receptor blockers give good results in hypertension， heart failure and other cardiovascular disorders. But they don’t give complete protection; there seems to be an effect which is not surmounted by standard RAS blockade. My postulate is that the local system， for example， the local system in the heart is itself very important in producing some of the pathophysiologic changes that are seen in disease and that inhibition of the circulating system isn’t going to do the job completely. What we need to do is understand better those local systems and attack them more specifically. Essentially there are enzymes involved in the heart including kinase which is very important in regulating local angiotensin II production which is much more important in the heart locally particularly than it is in circulation. So despite standard inhibition of the RAS with the standard drugs that are available you are still going to get a substantial amount of angiotensin II produced in the heart. If we can develop new drugs which target those other pathways including kinase， that may confer additional protective benefits.

　　Ferro教授：我演讲的主要内容是心脏局部RAAS的重要性。众所周知，循环RAAS在调节心血管功能方面发挥重要作用。RAAS是ACEI和ARB作用的靶点。ACEI和ARB在高血压、心力衰竭（心衰）和其他心血管疾病的治疗方面都有不错的疗效。但是，ACEI和ARB并不能够提供100%的保护；这两类药物的保护作用限于标准的RAAS阻断作用。我的假设是，局部RAAS（比如说心脏局部RAAS）本身在导致疾病的某些病理生理变化方面起着非常重要的作用。只抑制循环RAAS并不能达到100%的保护作用。我们需要做的是更深入地理解局部RAAS系统并更加有特异性地针对它。重要的是，心脏的一些激酶在调节局部血管紧张素II生成方面发挥重要作用，心脏局部的血管紧张素II生成要较循环中血管紧张素II的生成更为重要。因此，尽管给予标准的药物抑制RAAS，但是在心脏局部仍然有大量的血管紧张素II生成。如果我们能够研发出针对包括激酶等物质的其他通路的话，就可能为患者带来额外的保护作用。

　　<International Circulation>:  What exactly are we trying to protect against? Are we protecting against the progression to heart failure in hypertensive patients?

　　《国际循环》：我们要保护的是什么？是保护高血压患者不至于进展到心衰吗？

　　Dr Ferro: Yes. We are talking about prevention of hypertrophy in hypertension. We are talking about prevention of remodeling in heart failure. We are talking about the prevention of oxidative stress which is a very important effect of angiotensin II which gives rise to a whole series of pathophysiological changes in hearts. That is one of the main adverse things that angiotensin II does in disease. Essentially we are talking about inhibiting all of those things that are mediated by local production of angiotensin II.

　　Ferro博士：我们说的保护是在高血压患者预防心脏肥厚的发生，预防心衰时发生心室重构，预防氧化应激。引起氧化应激是血管紧张素II的一个非常重要的作用，这可能会导致心脏发生一系列的病理生理变化。这只是血管紧张素II在疾病中发挥的主要不良效应之一。我主要是指抑制那些由局部血管紧张素II生成所引起的不良后果。

　　<International Circulation>: How much is electrical remodeling affected by the local RAS? How much is atrial fibrillation affected by it?

　　《国际循环》：电重构对局部RAAS有多大的影响？电重构对房颤的影响有多大?

　　Dr Ferro: It is a difficult question to answer. I think it is affected but to what extent it is difficult to say for sure. I think it is not only going to be the remodeling; I think it is going to be things like reactive oxygen species which also affect electrical excitability which will predispose to things like AF and so on. It is a complex area.

　　Ferro教授：这个问题很难回答。我想是有影响的，但是很难确切地说出影响的程度到底有多大。我想不仅仅是重构的问题，活性氧产物等物质也会影响到心肌的电兴奋性，随后会使得发生房颤的风险增加。这是一个很复杂的研究领域。
　　<International Circulation>: Do you have any prospective treatments that might target the local system?

　　《国际循环》：针对局部RAAS有没有什么有前景的治疗手段？

　　Dr Ferro: I talked about direct renin inhibition as a possible way of doing that. And there is some circumstantial evidence that direct renin inhibition is doing things over and above what is standard RAS inhibition which the ACE inhibitors and ARBs are doing. I can’t give you convincing evidence that it is doing that by acting on the local system but my postulate is that a lot of what direct renin inhibition is doing is directed not just at the circulating system but the local system as well.

　　Ferro教授：我提到过直接肾素抑制剂是针对局部RAAS的有前景的治疗手段。有少量证据提示，直接肾素抑制剂的作用超出ACEI和ARB所具有的RAAS作用。直接肾素抑制剂作用于局部RAAS，这方面已经有令人信服的证据。我的假设是直接肾素抑制剂的大部分作用不仅仅是针对循环RAAS，还针对局部RAAS。