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Michael R. Jones, Jean E. Sealey, John H. Laragh, Effects of Angiotensin Receptor Blockers on Ambulatory Plasma Renin Activity in Healthy, Normal Subjects During Unrestricted Sodium Intake: , American Journal of Hypertension, Volume 20, Issue 8, August 2007, Pages 907–916, https://doi.org/10.1016/j.amjhyper.2007.04.009
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Abstract
Plasma renin activity (PRA), measured under controlled conditions, is a marker of the degree and persistence of renin-angiotensin system blockade.
Two similarly designed five-way crossover studies evaluated angiotensin II type 1 (AT1) receptor blockade-induced changes in PRA in quietly seated, ambulatory volunteers who were ingesting uncontrolled diets. At weekly intervals, PRA was measured during the 24 h after administration of placebo, olmesartan medoxomil (20 or 40 mg), or valsartan (80 or 160 mg) (Study CS866-445), or placebo, olmesartan medoxomil (40 mg), valsartan (160 or 320 mg), or irbesartan (300 mg) (Study CS866-448). The primary end point was change in PRA relative to placebo from predose to 24 h postdose (ΔPRA24).
In the 20 subjects who completed each study, there was a direct relationship between baseline PRA and ΔPRA24 for all doses. Subjects with low PRA (<0.65 ng/mL/h) exhibited very low absolute increases in PRA. The ΔPRA24 increased significantly with olmesartan medoxomil 20 mg (P < .01) and 40 mg (P < .001) and valsartan 160 mg (P < .05) but not with valsartan 80 mg. In the second study (in which baseline PRA was lower), ΔPRA24 increased with olmesartan medoxomil 40 mg (P < .0001), valsartan 320 mg (P < .01), and irbesartan 300 mg (P < .01) but not with valsartan 160 mg. The ΔPRA24 was greatest with olmesartan medoxomil 40 mg and was dose-related for olmesartan medoxomil but not for valsartan.
The greater ΔPRA24 with olmesartan medoxomil 40 mg indicates a more prolonged AT1 receptor blockade than with valsartan 80, 160, or 320 mg or irbesartan 300 mg. A routine, clinic ambulatory PRA level can be used as a biochemical marker of the persistence and degree of AT1 receptor blockade in subjects without suppressed PRA levels. Am J Hypertens 2007;20: 907–916 © 2007 American Journal of Hypertension, Ltd.
