Angiotensin receptor antagonists in experimental models of chronic renal failure.
The efficacy of angiotensin converting enzyme inhibitors (ACEI) in slowing the advancement of chronic renal disease attests to the importance of angiotensin II (Ang II) in the pathophysiological mechanisms underlying disease progression. It is apparent from studies of the effects of orally-active AT1 receptor antagonists (AT1RA) in experimental models of chronic progressive renal disease, that AT1RA have broadly similar effects to those of ACEI, implying that the favorable effects 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 AT1 receptors. The possibility remains, however, that differences in the modes of action of ACEI and AT1RA are significant in terms of renal protection and that the two classes of drugs are not therapeutically equivalent. Thus far, however, virtually all experimental studies comparing the renal protective effects of ACEI versus AT1RA have failed to show any convincing differences between the two classes of drug that cannot be attributed to discrepancies in the levels of blood pressure control achieved. As many rodent studies have adopted protocols originally designed to distinguish between the effects of treatment versus no treatment, however, it may be premature to conclude that ACEI and AT1RA are, essentially, therapeutically equivalent. Since both classes of drug have such potent renoprotective effects, the extent of injury that develops in treated rats may be so slight as to compromise the sensitivity of the experimental comparison. Fresh experimental approaches may be required to overcome this issue and resolve any outstanding questions concerning the therapeutic equivalence of AT1RA and ACEI in slowing the progression of renal disease.
Mackenzie
H S
HS
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Ots
M
M
Ziai
F
F
Lee
K W
KW
Kato
S
S
Brenner
B M
BM
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D051381:Rats
D057911:Angiotensin Receptor Antagonists; D000804:Angiotensin II