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

• Published in: American journal of hypertension Vol. 20; no. 8; pp. 907 - 916
• Main Authors: Jones, Michael R., Sealey, Jean E., Laragh, John H.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2007; Oxford University Press; Elsevier Science
• Subjects: Adolescent; Adult; Aged; Aldosterone - urine; Angiotensin II; Angiotensin II Type 1 Receptor Blockers - administration & dosage; Angiotensin receptor blocker; Antihypertensive agents; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Biomarkers - blood; Biomarkers - urine; Biphenyl Compounds - administration & dosage; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiology. Vascular system; Cardiovascular system; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Imidazoles - administration & dosage; irbesartan; Male; Medical sciences; Middle Aged; Olmesartan Medoxomil; Pharmacology. Drug treatments; PRA; Prognosis; Radioimmunoassay; Reference Values; Renin - blood; Renin - drug effects; renin-angiotensin system; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; Single-Blind Method; Sodium Chloride, Dietary - administration & dosage; Tetrazoles - administration & dosage; Valine - administration & dosage; Valine - analogs & derivatives; Valsartan; olmesartan medoxomil; valsartan; irbesartan; Angiotensin receptor blocker; renin-angiotensin system; PRA; Human; Hypertension; Tetrazole derivatives; Valsartan; Enzyme; Cardiovascular disease; AT1 angiotensin receptor; Olmesartan medoxomil; Peptidases; Renin angiotensin system; Renin; Irbesartan; Sodium; Biphenyl derivatives; Aminoacid; Hydrolases; Antihypertensive agent; Aspartic endopeptidases; Angiotensin antagonist; Ambulatory; Angiotensin II
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2007.04.009

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 (<0.65 ng/mL/h) exhibited very low absolute increases in PRA. The ΔPRA 24 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), ΔPRA 24 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 ΔPRA 24 was greatest with olmesartan medoxomil 40 mg and was dose-related for olmesartan medoxomil but not for valsartan. The greater ΔPRA 24 with olmesartan medoxomil 40 mg indicates a more prolonged AT 1 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 AT 1 receptor blockade in subjects without suppressed PRA levels.