Chronotherapy of hypertension

This chapter addresses the chronotherapy of hypertension. Chronotherapeutics is the purposeful timing of medications, whether or not they utilize special drug-release technology, to proportion their serum and tissue concentrations in synchrony with known circadian rhythms in disease processes and symptoms as a means of enhancing beneficial outcomes and/or attenuating or averting adverse effects (Smolensky and Haus, 2001). The concept of chronotherapeutics, although relatively new to hypertension and cardiovascular medicine, was first introduced and proven worthy in clinical medicine in the 1960s; the morning alternate-day corticosteroid tablet dosing schedule was introduced as a convenient means of minimizing the adverse effects of such anti-inflammatory medications as prednisone and methylprednisolone (Harter et al., 1963; Reinberg, 1989). The chronotherapy of hypertension takes into account the clinically relevant features of the 24h pattern of blood pressure (BP), e.g., the accelerated morning rise at the commencement of diurnal activity and the extent of decline during nighttime sleep, plus potential administration-time (circadian rhythm) determinants of the pharmacokinetics and dynamics of individual antihypertensive medications. Herein, we focus on the chronotherapy of hypertension; however, as necessary background we first present the major concepts and mechanisms of biological timekeeping