Angotensin (Ang) II type 1 (AT(1)) receptor antagonists are orally active d
rugs that specifically block the subtype 1 of Ang receptors. In contrast to
AT(1) receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors
block the actions of Ang II incompletely. Furthermore, the bradykinin-pote
ntiating effects of ACE inhibitors may contribute to the mechanism of actio
n of ACE inhibitors. Data in experimental animals suggest that AT(1) recept
or antagonists decrease the glomerular filtration rate (GFR) to a lesser de
gree than ACE inhibitors. The greater effect of ACE inhibitors in decreasin
g glomerular pressure was attenuated with a bradykinin antagonist. In rat m
odels of renal damage with proteinuria, acute reduction of proteinuria was
seen with ACE inhibitors but not with AT(1) receptor antagonists, whereas l
ong-term reductions of proteinuria were of similar magnitude with both agen
ts. Renal histology after several months revealed that AT(1) receptor antag
onists and ACE inhibitors were equally renoprotective in various renal dama
ge models. AT(1) receptor antagonists, like ACE inhibitors, exhibit a natri
uretic effect equal to moderate doses of a thiazide diuretic. In patients w
ith severe volume depletion, use of AT(1) receptor antagonists may lead to
acute renal failure. Valsartan was tested in a double-blind trial in patien
ts with moderate to severe renal failure and led to a substantial decrease
in diastolic and systolic blood pressure, whereas there was no difference f
rom placebo for changes in GFR. Urine protein increased with placebo and de
creased with valsartan. The data indicate that valsartan in renal failure p
atients is effective in lowering blood pressure while leaving renal excreto
ry function unaltered. Whether there is a renoprotective effect can only be
shown in long-term trials, which are under way.