ANGIOTENSIN RECEPTOR ANTAGONISTS IN EXPERIMENTAL-MODELS OF CHRONIC-RENAL-FAILURE

The efficacy of angiotensin converting enzyme inhibitors (ACEI) in slo wing the advancement of chronic renal disease attests to the importanc e of angiotensin II (Ang II) in the pathophysiological mechanisms unde rlying disease progression. It is apparent from studies of the effects of orally-active AT(1) receptor antagonists (AT(1)Ra) in experimental models of chronic progressive renal disease, that AT(1)RA have broadl y similar effects to those of ACEI, implying that the favorable effect s of ACEI on systemic and renal hemodynamics and indices of glomerular injury are mediated, in large part, by reducing the action of Ang II at AT(1) receptors. The possibility remains, however, that differences in the modes of action of ACEI and AT(1)RA are significant in terms o f renal protection and that the two classes of drugs are not therapeut ically equivalent. Thus far, however, virtually all experimental studi es comparing the renal protective effects of ACEI versus AT(1)RA have failed to show any convincing differences between the two classes of d rug that cannot be attributed to discrepancies in the levels of blood pressure control achieved. As many rodent studies have adopted protoco ls originally designed to distinguish between the effects of treatment versus no treatment, however, it may be premature to conclude that AC EI and AT(1)R4 are, essentially therapeutically equivalent. Since both classes of drug have such potent renoprotective effects, the extent o f injury that develops in treated rats may be so slight as to compromi se the sensitivity of the experimental comparison. Fresh experimental approaches may be required to overcome this issue and resolve any outs tanding questions concerning the therapeutic equivalence of AT(1)RA an d ACEI in slowing the progression of renal disease.