<International Circulation>: Would you please introduce which studies have shown olmesartan can lower blood pressure with stronger， earlier and smoother effects compared with other ARBs?
　　《国际循环》：有哪些研究显示傲坦与其他ARB相比较有更强效、更及时、更平稳的降压效果？
　　Prof. Zou Yun Zeng: I think I can discuss this question from three aspects. Firstly， olmesartan compared to other ARBs (Angiotensin II receptor blockers) has a better blood pressure lowering efficacy and there have been at least two studies to explain this effect I think we can know that Professor Oparil carried out the OPARIL Study which was a randomized， double blind controlled and multicentre clinical trial。The study compared the 4 ARBs: olmesartan， losartan， valsartan and irbesartan. They looked at systolic blood pressure effects of the different drugs and in their evaluation they found out that after 8 week treatment， olmesartan can best lower diastolic pressure than the three other ARBs. There were also different results among the 4 ARBs according to the values of the 24h dynamic blood pressure， 130/90mm/Hg as a goal after blood pressure treatment. For 8 weeks， 53% of the patients administered with olmesartan meet the blood pressure goal. And there was a statistically significant difference compared to other ARBs. Next is an meta-analysis of blood pressure lowering effects of ARBs， which highlighted differences between olmesartan and other ARBs。Different from other meta-analysis， this meta-study of ARBs has involved  the monitoring of dynamic blood pressure looking at 35 papers and found that compared to all the other ARBs olmesartan showed the best potential to lowering blood pressure and had significant differences regardless of diastolic and systolic pressure. The second explanation is that olmesartan is a quick onset ARB which can lower both systolic and diastolic blood pressure to more than 10% in 2 weeks uniquely among ARBs. The last one is olmesartan for the lowering of blood pressure especially lowering the morning blood pressure surge compared with valsartan and irbesartan：olmesartan decreases blood pressure more than 3-5mm of Hg/mm and therefore reduce the risk of cardiovascular events.
　　邹云增教授：可从3个方面探讨此问题。首先是奥美沙坦与其他ARBs对比降压效果更强。至少有2项研究证实了这一点，其中Oparil教授进行的随机、双盲、多中心的OPARIL试验对比了奥美沙坦、氯沙坦、缬沙坦和厄贝沙坦4种ARBs的疗效，发现治疗8周后奥美沙坦对收缩压的降低优于其他3种药物；同时以130/90 mmHg为目标水平评价24 h动态血压，8周后奥美沙坦的达标率为53%，显著优于另3种ARBs。其次，有关ARBs降压效应的一项荟萃分析，显示了奥美沙坦与其他ARBs的不同。与其他荟萃分析不同，这项分析纳入了监测动态血压的35篇文献，发现无论是收缩压还是舒张压奥美沙坦都是降压效应最强的ARB；此外，奥美沙坦起效迅速，还是唯一可在2周内使收缩压和舒张压降低>10%的ARB。最后，奥美沙坦较其他ARB可更好地控制晨间血压，使之进一步降低3~5 mmHg，从而减少心血管事件的发生。

　　<International Circulation>:  It has been proven that olmesartan is superior to placebo， diuretic， and other ARBs in lowering BP. What are the deterninants making olmesartan the strongest anti-hypertensive ARB?
　　《国际循环》：奥美沙坦与安慰剂、利尿剂及其他ARB制剂的对比研究已证实其降压疗效具有明显优势，您认为那些因素决定了奥美沙坦成为最强效的ARB药物？
　　Prof. Zou Yun Zeng: I think I can explain the effects of olmesartan from three aspects. Firstly， it has a unique molecular structure and its effector mechanisms make olmesartan the strongest anti-hypertensive ARB. Olmesartan is the only ARB with double chain domains which are related to tightly and irreversibly binding to the AT-1 receptor and is important in inducing reverse agonism. Secondly， olmesartan exhibits its effects completely on the AT-1 receptor which can induce it towards full inactivity. Thirdly， is due to the binding way of the ARB， olmesartan can be dissociated by its ability to bind to the AT-1 receptor and this association is highest among all ARBs. This ability of olmesartan to block both the angiotensin II dependent and independent signaling pathways and being stronger in blocking signals than other ARBs makes it a very strong ARB.
　　邹云增教授：可以从3个方面解释这一效应。首先，奥美沙坦独特的分子结构和作用机制使其成为最强效的抗高血压ARB，其唯一具有的双侧链活性区域决定了其与AT1受体的不可逆紧密结合，这对其反向激动作用至关重要。其次，奥美沙坦对AT1受体的完全作用，致其完全失活。第三，就是奥美沙坦与AT1受体不可解离的结合方式，决定了奥美沙坦可阻断AT II依赖和非依赖性的信号旁路，从而使其成为较其他ARBs更强效的ARB。

　　<International Circulation>: How to understand the mechanism of AT1 receptor reverse agonism by olmesartan?
　　《国际循环》：如何理解奥美沙坦的反向激动机制？
　　Professor Zou Yun Zeng: I think I can also explain this from three aspects. Generally， AT-1 has three situations we can note: fully active，partially active and fully inactive states. When angiotenson II binds to the AT-1 receptor there will be a conformational change of the AT-1 to a fully active state. However， angiotensin 1 is not the only agonist for the AT-1 receptor  .According to old and other studies the mechanical stress such as hypertension could also induce the AT-1 receptor into a partially active state even when there is no angiotensin II the mechanical stressed AT-1 receptor itself has constitutive activity. Secondly， other ARBs can only inhibit the activity induced by angiotensin II but not inhibit the activity induced by the mechanical stress and AT-1 receptor constitutive activity. Thirdly， olmesartan can not only inhibit the activity induced by angiotensin II but can also inhibit the mechanical stress but also AT-1 receptor constitutive activity which can bring the AT-1 receptor into a fully inactive state. I think this is the effect of olmesartan complete reverse agonism and also underlying mechanism of olmesartan makes it the strongest ARB.
　　邹云增教授：仍然可以从3个方面解释这一问题。通常AT1有3种状态：完全活性、部分活性和完全失活状态。当AT II结合于AT1受体时，AT1受体发生构象改变、完全活化。但AT II 不仅是AT1受体激动剂。根据既往研究，机械应力如高血压可诱导AT1受体转为部分活性状态，即使没有AT II，机械应力下AT1受体本身也具有组织活性。第二，其他ARB仅能抑制AT II诱导的AT1活性，不能抑制机械应力诱导的以及AT1受体组织活性。第三，奥美沙坦不仅抑制AT II诱导的AT1活性，而且抑制机械应力诱导的和AT1受体自身组织活性，使其完全失活。这是奥美沙坦的完全反向激动效应，也是其成为最强效ARB的潜在机制。

　　<International Circulation>:  Does olmesartan has better organ protection effect