ACE-I vs angiotensin II receptor antagonists: prevention of renal injury in chronic rat models

There is now abundant evidence that treatment with angiotensin-converting e nzyme inhibitors (ACE-I) ameliorates the progression of chronic renal disea se. Attention has therefore focused on the role of the renin angiotensin-al dosterone (RAA) system in mediating the development of progressive glomerul osclerosis and angiotensin II (Ang It) has been implicated in several proce sses thought to be important in the pathogenesis of this entity. Conversely , ACE is also known to catalyse the breakdown of bradykinin. Thus, ACE-I tr eatment results in elevated bradykinin levels which may cause selective eff erent arteriolar dilatation, suggesting an alternative explanation for the beneficial effects of this class of drugs in chronic renal disease. The dev elopment of specific angiotensin type 1 receptor antagonists (AT(1)RA) has provided a means of testing the relative importance of these two mechanisms . In addition, AT(1)RAs differ from ACE-I in their effect on the RAA system in other aspects which may represent therapeutic advantages. This paper re views studies which have compared ACE-I and AT(1)RAs in several rat models of chronic renal disease. Most have found similar beneficial effects includ ing amelioration of proteinuria and glomerulosclerosis, which suggests that the effects of ACE-I are due to a reduction in Ang II activity and not due to increased levels of bradykinin, One long-term study has suggested great er renal protection with candesartan than with enalapril, However, conclusi ons as regards the relative efficacy of these two groups of agents in ameli orating the progression of chronic renal disease await the results of furth er long-term studies.