International Circulation: Plasma renin activity is an important predictor of cardiovascular events and we know that aliskiren can reduce PRA quite effectively.  What clinical outcome does this reduced PRA lead to?

《国际循环》：血浆肾素活性是心血管事件的重要预测因素，我们知道，阿利克仑可以相当有效地降低血浆肾素活性。请问降低血浆肾素活性可以得到什么临床结果？

GT McGuiness:  Renin clearly has a very important role in the renin-angiotensin system， hence the name.   We have in the past felt that it was an upstream effect， in other words， affects in renin resulted in changes in angiotensin generation and it was angiotensin II which was the ‘bad guy’ in all of this.  That was probably true.  However， recently we have recognized that renin itself， plasma renin， active renin may have detrimental effects in tissues.  Since blocking both using an ACE inhibitor and an angiotensin receptor blocker in combination would tend to increase plasma renin activity， this may be one of the ways whereby we are not achieving as much as we could achieve by blocking the system.  It is important to recognize that direct renin inhibition is also associated with an increase in renin levels but it is not active renin.  That is the key difference because direct renin inhibitors prevent this conversion of inactive renin into active renin， we do not see rises in active renin and， therefore， we do not see the potential harm that we see with the other classes.

GT McInnes教授：很清楚，肾素在肾素-血管紧张素系统中起到重要作用，因此这一系统以此命名。我们以前认为，肾素产生上游效应，换句话说，改变肾素水平可导致血管紧张素的生成出现变化，血管紧张素II被认为是这一系统产生有害作用的原因。这可能是正确的。然而，最近我们意识到，活性肾素可能对组织产生负性效应。联合使用ACE抑制剂和血管紧张素受体阻滞剂是阻断RAS系统的一种方法，但并没有获得非常好的效果。但是这种联合可以升高血浆肾素活性，非常重要的一点是，直接的肾素抑制剂也可能升高肾素水平，但不是活性肾素的水平。这是它们有所区别的关键，因为直接肾素抑制剂可防止无活性肾素转变为活性肾素，我们没有观察到活性肾素水平升高，因此，我们没有看到它的潜在危害，但我们在其他种类的药物中却可以看到这种危害。