Angiotensin II receptor blockade in normotensive subjects - A direct comparison of three AT(1) receptor antagonists

Use of angiotensin (Ang) II AT(1) receptor antagonists for treatment of hyp ertension is rapidly increasing, yet direct comparisons of the relative eff icacy of antagonists to block the renin-angiotensin system in humans are la cking. In this study. the Ang II receptor blockade induced by the recommend ed starting dose of 3 antagonists was evaluated in normotensive subjects in a double-blind, placebo-controlled, randomized, 4-way crossover study. At 1-week intervals, 12 subjects received a single dose of losartan (50 mg), v alsartan (80 mg), irbesartan (150 mg) or placebo. Blockade of the renin-ang iotensin system was assessed before and 4, 24, and 30 hours after drug inta ke by 3 independent methods: inhibition of the blood pressure response to e xogenous Ang II, in vitro Ang II receptor assay, and reactive changes in pl asma Ang II levels. At 4 hours, losartan blocked 43% of the Ang II-induced systolic blood pressure increase; valsartan, 51%; and irbesartan, 88% (P<0. 01 between drugs). The effect of each drug declined with time. At 24 hours, a residual effect was found with all 3 drugs, but at 30 hours, only irbesa rtan induced a marked, significant blockade versus placebo. Similar results were obtained when Ang II receptor blockade was assessed with an in vitro receptor assay and by the reactive rise in plasma Ang II levels. This study thus demonstrates thy the first administration of the recommended starting dose of irbesartan induces a greater and longer lasting Ang II receptor bl ockade than that of valsartan and losartan in normotensive subjects.