Figure 614

Renin-angiotensin systems. For many reasons the effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (AII) type 1 AT1 receptor antagonists on the progression of chronic renal disease may not be identical. In the classic pathway, renin cleaves angiotensinogen to form AI, which is further cleaved by ACE to form biologically active AII. ACE inhibitors inhibit the renin-angiotensin system by reducing the activity of ACE and decreasing AII formation. ACE also catalyzes other important pathways, however, including the breakdown of vasodilator substances such as bradykinin, substance P, and enkephalin. Increased levels of these substances might account for some of the biologic effects of ACE inhibition. Levels of these substances would not increase after administration of an AT1 receptor antagonist. In contrast, inhibition of the renin-angiotensin system by ACE inhibitors may be incomplete because other proteases may catalyze to conversion of angio-tensinogen to AII (on the right). CAGE— chymostatin-sensitive angiotensin II-generating enzyme; t-PA—tissue plasminogen activator. (Adapted from Dzau and coworkers [14].)

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