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Administration–time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension

Smolensky, Michael H.a; Hermida, Ramón C.b; Ayala, Diana E.b; Tiseo, Ruanac; Portaluppi, Francescoc

doi: 10.1097/MBP.0b013e32833c7308

There is growing interest on how to best tailor blood pressure (BP)-lowering medications according to the circadian (24 h) BP pattern of individual patients, that is, chronotherapy. Significant and clinically meaningful treatment–time differences in the beneficial and/or adverse effects of at least six different classes of hypertension medications are now known. Generally, calcium channel blockers are more effective with bedtime than morning dosing, and in the case of dihydropyridine derivatives bedtime dosing significantly reduces the risk of edema. Scheduling angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors at bedtime, as opposed to awakening, increases the proportion of patients with properly controlled BP, enhances the sleep-time relative BP decline towards a normal dipping pattern and best reduces urinary albumin excretion, a marker of functional renal status. The chronotherapy of conventional BP-lowering medications entails their correct scheduling with reference to the body's circadian rhythms, not only to achieve control of daytime and night-time systolic and diastolic BP but to normalize the dipping status of the 24 h pattern. Chronotherapy constitutes a cost-effective strategy for enhancing BP control during both nocturnal sleep and daytime activity and for potentially reducing the risk of cardiovascular disease and end-organ injury of the blood vessels and tissue of the heart, brain, kidney, eye and other organs.

aDepartment of Biomedical Engineering, The University of Texas at Austin, Texas, USA

bBioengineering and Chronobiology Laboratories, University of Vigo, Campus Universitario, Vigo, Spain

cDepartment of Clinical and Experimental Medicine, Hypertension Center, University Hospital S. Anna, University of Ferrara, Ferrara, Italy

Correspondence to Michael H. Smolensky, PhD, The University of Texas-Houston Health Sciences Center, 808 Lakewood Hills Terrace, Austin, Texas 78732, USA

Tel: +1 512 266 0894; e-mail:

Received 10 February 2010 Revised 30 April 2010 Accepted 13 May 2010

© 2010 Lippincott Williams & Wilkins, Inc.