Effects of Angiotensin Receptor Blockers on Ambulatory Plasma Renin Activity in Healthy, Normal Subjects During Unrestricted Sodium Intake

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 (AT 1) 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 (ΔPRA 24). In the 20 subjects who completed each study, there was a direct relationship between baseline PRA and ΔPRA 24 for all doses. Subjects with low PRA (