Angiotensin II receptor blockade in normotensive subjects: A direct comparison of three AT1 receptor antagonists.

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Mazzolai L, Maillard M, Rossat J, Nussberger J, Brunner HR, Burnier M

Angiotensin II receptor blockade in normotensive subjects: A direct comparison of three AT1 receptor antagonists.

Hypertension. 1999 Mar;33(3):850-5.

PubMed ID

10082498 [ View in PubMed

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Abstract

Use of angiotensin (Ang) II AT1 receptor antagonists for treatment of hypertension is rapidly increasing, yet direct comparisons of the relative efficacy of antagonists to block the renin-angiotensin system in humans are lacking. In this study, the Ang II receptor blockade induced by the recommended 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), valsartan (80 mg), irbesartan (150 mg), or placebo. Blockade of the renin-angiotensin system was assessed before and 4, 24, and 30 hours after drug intake by 3 independent methods: inhibition of the blood pressure response to exogenous Ang II, in vitro Ang II receptor assay, and reactive changes in plasma 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 irbesartan 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 that the first administration of the recommended starting dose of irbesartan induces a greater and longer lasting Ang II receptor blockade than that of valsartan and losartan in normotensive subjects.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Irbesartan	Type-1 angiotensin II receptor	Protein	Humans	Yes	Antagonist	Details

Pharmaco-proteomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Irbesartan	Approved Investigational	AGT	183	increased	irbesartan results in increased expression of AGT protein	1q42.2
Irbesartan	Approved Investigational	AGT	183	increased	irbesartan results in increased expression of AGT protein	1q42.2
Valsartan	Approved Investigational	AGT	183	increased	Valsartan results in increased expression of AGT protein	1q42.2
Valsartan	Approved Investigational	AGT	183	increased	Valsartan results in increased expression of AGT protein	1q42.2
Losartan	Approved	AGT	183	increased	Losartan results in increased expression of AGT protein	1q42.2
Losartan	Approved	AGT	183	increased	Losartan results in increased expression of AGT protein	1q42.2
Losartan	Approved	AGT	183	increased	Losartan results in increased expression of AGT protein	1q42.2