<International Circulation>: It has been shown that olmesartan is superior to placebo， diuretic， and other ARBs in lowering BP. Are there any particular factors that make olmesartan a stronger ARB?
　　《国际循环》：研究已证实奥美沙坦降低BP优于安慰剂、利尿剂和其他ARB类药物。哪些特殊因素使得奥美沙坦成为降压作用更强的ARB？
　　Prof. Zhu : Compared to other ARBs， olmesartan has the strongest effects of BP lowering. I think that this is due to the unique molecular structure of the drug. Olmesartan has a hydroxyl group in addition to a carboxyl group; the latter is uncommon in other ARBs. We call this a double-chain domain. Due to this unique molecular structure， olmesartan binds to the AT1 receptor more tightly and has an insurmountable property. In addition， this structure confers olmesartan with an inverse agonism. Recently， it was found that the activation of the AT1 receptor can be induced by a mechanical stress and this is without angiotensin II.  An inverse agonist can inhibit this AT1 receptor activation， so olmesartan can inhibit both the constitutive activation of the receptor and also the angiotensin II independent activation. Therefore， this drug has very strong effects on BP lowering.
　　朱鼎良教授：与其他ARB相比，奥美沙坦有最强的降压作用。我认为这归因于该药物独特的分子结构。奥美沙坦有一个羟基和一个羧基，后者是多数其他ARB所不具有的，也就是我们所说的“双链区域”。由于这一独特的分子结构，奥美沙坦与AT1受体的结合更为紧密，使其具有不可超越的性能。另外，这一结构赋予奥美沙坦独特的反向激动作用。近期研究发现，机械应力可独立于血管紧张素II（AT II）而诱导AT1受体的激活。反向激动剂可抑制这种AT1受体激活。因此，奥美沙坦不但可抑制AT1受体的结构性激活，还可抑制独立于AT II的激活。因此，该药物有更强的降压作用。

　　<International Circulation>: Professor Ritz， we know that you were a member of the steering committee of the ROADMAP trial and so we would be especially interested in your views of this trial. A pos-hoc analysis of ROADMAP demonstrated a “substantial BP-independent effect” of olmesartan in preventing microalbuminuria. What is in the intrinsic mechanism of this benefit?
　　《国际循环》：Ritz教授，您是ROADMAP试验指导委员会成员，因此我们十分感兴趣您对该试验的看法。ROADMAP事后分析显示奥美沙坦预防微量白蛋白尿（MAU）具有“可观的独立于BP之外的作用”。这一获益的内在机制是什么？
　　Prof. Ritz: Microalbuminuria is of course the predictor of the first stage of progressive diabetic nephropathy. I think the most important aspect of the ROADMAP study that we discussed today is the fact that evidence was provided that within the range of normotensive values， in contrast to the previous trial with the ACEI trandolapril， there is still a virtually blood pressure independent effect on the de novo appearance of microalbuminuria. Therefore， if we accept that microalbuminuria is a powerful predictor of the future fate of the diabetic patient with respect to renal and cardiovascular complications， then this is very good news. It is wise in pharmacology to look at the compounds for which benefit has been proven and this is the first proof that lowering blood pressure in the normotensive range still provides additional benefit on the development of microalbuminuria in the diabetic individual. This is a breakthrough observation and it is hopeful that the same benefit will be seen with respect to retinal changes and macrovascular cardiac changes， which have not been the object of the ROADMAP study.
　　Eberhard Ritz教授：当然，MAU是进展性糖尿病肾病第一阶段的预测因子。我认为，我们今天讨论的ROADMAP研究最重要的方面是在正常血压范围内提供了证据：相对于以往采用ACEI群多普利的试验，奥美沙坦在预防MAU发生方面存在一种实质上独立于血压的影响。因此，如果我们接受MAU是糖尿病患者肾脏和心血管并发症未来命运的一个强预测因子，那么这是非常好的消息。在药理上，考虑获益已经得到证实的药物是明智的，ROADMAP首次证明在糖尿病个体中，正常血压范围内降压对预防MAU发生仍能提供额外的获益。这是一项突破性的观察，同样的获益有望见于并未被列为ROADMAP 研究目的的视网膜改变和心脏大血管改变。

　　<International Circulation>:  What is the latest progress in studying olmesartan-based combination therapy? Also， are there any special benefits of an olmesartan-based combination compared to other ARB-based combinations?
　　《国际循环》：基于奥美沙坦的联合治疗研究方面有哪些最新进展？另外，与基于其他ARB的联合治疗相比，基于奥美沙坦的联合治疗有何特别获益？
　　Prof. Zhu: Most hypertensive patients need combination therapy to achieve BP goal. The combination of olmesartan with a diuretic has a stronger effect on BP lowering compared to olmesartan or diuretic alone. Recently， a combination of olmesartan and amlodipine has become available. I think this is the best combination for treatment of hypertension since olmesartan and amlodipine have very potent blood pressure lowering effects. Also， this combination can decrease the side effects of amlodipine such as edema.
　　朱鼎良教授：大多数高血压患者都需要联合治疗实现BP达标。与单用奥美沙坦或利尿剂相比，奥美沙坦与利尿剂联合有更强的降压效应。近期研究了奥美沙坦与氨氯地平联合疗法。我认为这是治疗高血压的最佳组合，因为奥美沙坦和氨氯地平均有着极强的降压作用。此外，这一组合可降低氨氯地平的不良反应如水肿。

　　<International Circulation>:  Professor Ritz， what is your view of the combination of olmesartan with either amlodipine or HCTZ?
　　《国际循环》：Ritz教授，您对奥美沙坦联合氨氯地平或HCTZ持何种观点？
　　Prof. Ritz: It is not surprising that a diuretic will amplify and increase the effectiveness of an inhibitor of the renin-angiotensin system. With respect to combination therapy， it is virtually impossible to get a diabetic patient normotensive with monotherapy and even the combination with a diuretic is most frequently not sufficient. A calcium channel blocker is an extremely wise combination in view of the recent paper by Dr. Michael Weber and others in the New England Journal of Medicine that showed， in contrast to past recommendations by the NIH， the combination of RAS blockade with amlodipine is more effective than combination with a diuretic.
　　Eberhard Ritz教授：利尿剂扩大或增加RAS抑制剂的效应并不奇怪。联合治疗方面，要采用单药治疗使糖尿病患者血压正常几乎是不可能的，即使与利尿剂联合也常常是不够的。Dr. Michael Weber和其他人近期发表在《新英格兰医学杂志》上的文章观点是，钙通道阻滞剂是一种非常明智的组合对象，该文章显示，相对于NI