International Circulation: I’d like to talk about direct renin inhibition.  Could you please discuss a bit about the mechanism its role in anti-hypertensive therapy and cardio-renal protection?

《国际循环》：我想和您谈谈直接的肾素抑制剂方面的问题。请您谈谈这类药物发挥抗高血压作用和心肾保护效应的机制。

GT McGuiness:  Direct renin inhibition has got some prospects to offer some real advantages in blocking the renin-angiotensin system.  We can now block the renin-angiotensin system at three levels.  The first widely used approach was to block the conversion of angiotensin I into angiotensin II.  The more recent development was actually acting at the angiotensin receptor， more selectively at the AT1-receptor.  Both of these approaches have shown real promise in the treatment of cardiovascular disease (CVD).  From a pharmacologist’s point of view， the most appropriate place to block the system is at the rate-limiting step， which is where renin works.  Renin acts on angiotensinogen to generate angiotensin I， and this is the rate-limiting step in the process， therefore offering the prospect of the more complete blockade of the system than was achieved with these other blockade approaches， which to some extend resulted in other compensatory changes in the system， offsetting their benefit.  

GT McInnes教授：直接的肾素抑制剂在阻断肾素-血管紧张素系统方面具有一定的优势，并且已经展现出了应用前景。我们现在可以在3个水平上阻断肾素-血管紧张素系统。首先广泛应用的方法是阻断血管紧张素I向血管紧张素II的转换。较新的方法是作用于血管紧张素受体，更加有选择性地作用于AT1受体。这两种方法对心血管疾病的治疗已经显示出了很好的结果。从药理专家的观点来看，阻断这一系统的最恰当途径是作用于限速步骤，也就是对肾素直接进行阻断。肾素作用于血管紧张素原，使之形成血管紧张素I，这是整个RAAS系统中的限速步骤，因此直接抑制肾素可以比阻断其他环节更完全地抑制RAAS系统，而在RAAS系统的其他环节进行阻断在一定程度上可代偿性导致肾素升高，而这种变化部分抵消了其应得的益处。

International Circulation:  So this approach then helps to avoid some of the compensatory changes that would offset the benefit?

《国际循环》：那么这种方法是否有助于避免一些代偿变化？因为这些代偿改变可能抵消某些益处。

GT McGuiness:  Yes， in particular the increase in renin that we see with these other agents and we do not see with the direct renin inhibitors.

 GT McInnes教授：是的，特别是我们看到，其他药物可导致肾素水平升高，但我们没有发现直接的肾素抑制剂可导致这种情况。

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