Assessment of angiotensin II receptor blockade in humans using a standardized angiotensin II receptor-binding assay.

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Serval ID
serval:BIB_5EE756EA6CCB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Assessment of angiotensin II receptor blockade in humans using a standardized angiotensin II receptor-binding assay.
Journal
American journal of hypertension
Author(s)
Maillard M.P., Mazzolai L., Daven V., Centeno C., Nussberger J., Brunner H.R., Burnier M.
ISSN
0895-7061
Publication state
Published
Issued date
1999
Peer-reviewed
Oui
Volume
12
Number
12 Pt 1-2
Pages
1201-8
Language
english
Notes
Publication types: Clinical Trial ; Comparative Study ; Journal Article ; Randomized Controlled Trial - Publication Status: ppublish
Abstract
An in vitro angiotensin II (AngII) receptor-binding assay was developed to monitor the degree of receptor blockade in standardized conditions. This in vitro method was validated by comparing its results with those obtained in vivo with the injection of exogenous AngII and the measurement of the AngII-induced changes in systolic blood pressure. For this purpose, 12 normotensive subjects were enrolled in a double-blind, four-way cross-over study comparing the AngII receptor blockade induced by a single oral dose of losartan (50 mg), valsartan (80 mg), irbesartan (150 mg), and placebo. A significant linear relationship between the two methods was found (r = 0.723, n = 191, P<.001). However, there exists a wide scatter of the in vivo data in the absence of active AngII receptor blockade. Thus, the relationship between the two methods is markedly improved (r = 0.87, n = 47, P<.001) when only measurements done 4 h after administration of the drugs are considered (maximal antagonist activity observed in vivo) suggesting that the two methods are equally effective in assessing the degree of AT-1 receptor blockade, but with a greatly reduced variability in the in vitro assay. In addition, the pharmacokinetic/pharmacodynamic analysis performed with the three antagonists suggest that the AT-1 receptor-binding assay works as a bioassay that integrates the antagonistic property of all active drug components of the plasma. This standardized in vitro-binding assay represents a simple, reproducible, and precise tool to characterize the pharmacodynamic profile of AngII receptor antagonists in humans.
Keywords
Angiotensin II, Antihypertensive Agents, Biological Markers, Biphenyl Compounds, Blood Pressure, Cross-Over Studies, Double-Blind Method, Humans, Hypertension, Losartan, Radioligand Assay, Receptor, Angiotensin, Type 1, Receptor, Angiotensin, Type 2, Receptors, Angiotensin, Reproducibility of Results, Tetrazoles, Valine, Vasoconstrictor Agents
Pubmed
Web of science
Open Access
Yes
Create date
05/03/2008 17:40
Last modification date
25/09/2019 7:09
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