<International Circulation>: How does RAAS activation of hypertension interact and finally lead to target organ damage?
　　Prof. Bakris: The renin-angiotensin-aldosterone system is a system， along with the sympathetic nervous system and along with natriuretic peptides and along with the kidneys， which are systems that are built into our bodies to modulate sodium， pressure changes and cellular function. Aldosterone， for example， is a hormone that is produced by the adrenal gland in response to changes in sodium and basically modulates the amount the salt that is in our system. If it goes up too high， it raises blood pressure and dumps potassium and has a lot of adverse consequences. If you block that， you retain potassium， prevent fibrosis certainly in the heart and kidney and we have very good data for that， and there are a lot of plus benefits. The older you get， the less activated that system is. The more salt you eat， the less activated that system is. If you have somebody who is eating a lot of salt and you give them a drug that blocks that system and look at blood pressure， you will find a very small response. If you then take the same patient and exclude all salt and take away everything that is suppressing that system and then wait a couple of weeks， there will be a nice blood pressure lowering because you have activated that system now and the drug is able to work on that system now because it is now activated. By the way， this system does not work in a vacuum. It interacts with the sympathetic nervous system so if this system is activated， the sympathetic system is also activated. If the sympathetic nervous system is activated the next system， whether it be the kidney or heart or so forth， is going to be activated to a certain degree. Depending on how you inhibited it， if you inhibit the RAAS you softly inhibit the sympathetic nervous system; not dramatically， but to a certain extent. In fact， beta-blockers， which are well-known drugs that lower blood pressure and that are specifically indicated for coronary disease or heart failure， because they work by lowering pressure by inhibiting renin， the key enzyme which stimulates the RAAS， down-regulates that system. They have different roles. If you leave that system unopposed over time， then you will get more vascular injury， more likelihood of fibrosis， more stiffness and a number of adverse changes. But this takes years; they don’t happen overnight or in a month. It is a long-standing situation. The key is if you really look at the evidence， blockers of the renin-angiotensin system as drugs are game changers. If you are really hardcore and only look at the evidence， you are only going to find that they are very effective in advanced kidney disease， in heart failure and to a lesser extent， after a heart attack. That’s it. Do they prevent kidney disease? No， there is very good evidence they don’t prevent kidney disease. Do they prevent retinopathy in diabetes? There is pretty good evidence that they do or dramatically change the natural history. You have to have a lot of sickness on board if you are using these drugs to actually show protection. That doesn’t mean that these drugs don’t lower blood pressure if you are not that sick， because they do. They are well-tolerated， especially the angiotensin receptor blockers. They are placebo-like in their side effects; dosing at the maximal dose is not a problem. When we come down to it， it is all about preventing the rise in pressure; it is the pressure cooker. If you are watching the pressure cooker， before the steam starts flying out everywhere， you can turn the heat down and still be well-cooked without the risk of the lid exploding.

　　《国际循环》：高血压时RAAS系统各部分是如何相互作用的？其激活是如何导致靶器官损害的？
　　Bakris教授：肾素——血管紧张素-醛固酮系统与肾交感神经系统、利钠肽、肾脏共同构成机体调节钠、压力变化及细胞功能的系统。例如，钠含量变化时，肾上腺将产生醛固酮，来调节钠盐含量。如果钠盐含量极度升高，血压将升高，导致钾排出，从而产生一系列的不良后果。如果能够阻止钠盐的升高，则能够使钾储留，从而预防心脏及肾脏的纤维化，并带来其他的额外获益。随着年龄的增长，该系统的活化度降低。饮食中摄入的盐越多，该系统的活性将越低。如果一个患者饮食中摄入了大量的食盐，开可阻断该系统的药物，其降压作用是非常弱的。同一个患者，控制饮食中钠盐摄入，并去除其他抑制该系统的因素后，应用该系统抑制剂几周后即能将其血压控制好，这是因为只有在激活该系统后，药物才发挥作用。顺便说一下，该系统在真空条件下不会发挥作用。它能与交感神经系统相互作用，因此当RAAS系统被激活时，交感神经系统也会被激活，从而使肾脏或心脏等在某种程度上被激活。轻度抑制RAAS系统可在一定程度上抑制，但无法显著抑制交感神经系统，实际上，常用降压药β受体阻滞剂，适用于冠状动脉疾病或心力衰竭患者，能够通过抑制肾素下调RAAS系统从而发挥作用。如果RAAS系统持续激活，将引发更多的血管损伤，更易发生纤维化、僵硬及很多不良改变。但是这个过程需要数年的时间， 不会一夜之间发生，也不会一个月内就发生，而是一个长期的过程。关键是RAAS阻断剂能够改变这些情况，其在预防心力衰竭及心脏病发作等方面是非常有效的。但是其不能预防肾脏疾病，能够显著预防糖尿病视网膜病变。它们的耐受性很好，副作用与安慰剂相当，因此应用最大剂量没有问题。

　　<International Circulation>: Do you have any final words as your term as ASH President comes to a close?
　　Prof. Bakris: We are all learning nuances about changes in blood pressure. I could go on here with data from ambulatory blood pressure monitoring that we still don’t understand that results in things that we are calling x but maybe y. We are learning a lot more about vascular compliance. I think that ASH is providing a forum for the nuances of these changes and explanations for the hypertension specialist and for the specialist who has an interest in this which enables them to catch up and go from there. The Society has expanded; it has a broader mission than it did even five or six years ago. It is the voice of hypertension and it is certainly going to continue in that vein. My successor has worked hand-in-hand with me and we are of the same mindset， so I am pretty confident that for the next two years at least， we are going to have further growth in the direction I have started in. Hopefully after that， every year is a new year with new challenges and new visions but I think we are doing well and I hope we are going to continue to do well.

　　《国际循环》：在您ASH主席任期结束时，最后您想说些什么？
　　Bakris教授：我们正在不断地了解血压变化的细微之处。我想谈一下动态血压监测，同时我们对血管顺应性有了更多的理解。我认为，ASH正为高血压专家及对该领域感兴趣的专业人士提供了解这些细微变化的平台。近年来，学会不断发展壮大，其使命更加广泛。我们关注高血压，也将继续关注静脉疾病。我的继任者与我并肩工作了很长时间，拥有相同的抱负。我确信至少未来两年内，我们将在既有方向上进一步发展壮大。此后，每年我们都将面临新的挑战，但是我相信我们能够继续将工作做好。
 

上一页  [1]  [2]  [3]