Fig. 11.

Proposed mechanism of how renin-angiotensin system (RAS) blockers work, even when not lowering the tissue levels of angiotensin (Ang) II. Normally, Ang II generation occurs in a highly localized manner by angiotensin-converting enzyme (ACE), allowing local Ang II type 1 receptor (AT₁R) stimulation. After treatment with an AT₁R (ARB) or ACE inhibitor (ACEI), this is no longer possible, although upregulation of ACE and AT₁R expression at alternative sites may occur, thus still allowing Ang II formation and AT₁R stimulation but in a less efficient (‘diluted’) manner.