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

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 AngI I-induced changes in systolic blood pressure. For this purpose, 12 normoten sive subjects were enrolled in a double-blind, four-way cross-over study co mparing the AngII receptor blockade induced by a single oral dose of losart an (50 mg), valsartan (80 mg), irbesartan (150 mg), and placebo. A signific ant linear relationship between the two methods was found (r = 0.723, n = 1 91, P < .001). However, there exists a wide scatter of the in vivo data in the absence of active AngII receptor blockade. Thus, the relationship betwe en the two methods is markedly improved (r = 0.87, n = 47, P < .001) when o nly measurements done 4 h after administration of the drugs are considered (maximal antagonist activity observed in vivo) suggesting that the two meth ods 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 ant agonists suggest that the AT-1 receptor-binding assay works as a bioassay t hat integrates the antagonistic property of all active drug components of t he plasma. This standardized in vitro-binding assay represents a simple, re producible, and precise tool to characterize the pharmacodynamic profile of AngII receptor antagonists in humans. Am J Hypertens 1999;12:1201-1208 (C) 1999 American Journal of Hypertension, Ltd.