These changes progressively increase from lighter to deeper stages of NREM, i.e. sleep stages N1 through N3. BP, HR, cardiac output and peripheral vascular resistance all decrease in NREM stages 1 through 3 10,11 . Thus, BP normally shows a "dipping" pattern at night 12 .
REM sleepIn rapid eye movement (REM) sleep, there is a reduction in tone of the respiratory muscles except for the diaphragm 13 . Simultaneously, a decrease in sensitivity of the central chemoreceptors occurs 14 . Consequently, ventilation decreases to levels even lower than that seen during NREM sleep and PaCO2 levels start to rise. Sympathetic tone increases during tonic REM sleep, with intermittent surges in both sympathetic and parasympathetic activation during phasic REM, with marked BP and HR fluctuations, such that the overall BP and HR in REM sleep are similar to the levels seen during wakefulness 10 .
WakefulnessAn "arousal" from sleep is represented by a change in the electroencephalogram for <10 seconds, and if this change is prolonged for 10 or more seconds, it is termed as an "awakening" 15 . During arousals and awakenings from sleep, sudden increases in minute ventilation, HR and BP are noted 16,17 . Some degree of ventilatory "overshoot" occurs in that the increase in respiratory drive during arousals and awakenings is higher than that expected for the PaCO2 level at the time 16 . A rise in sympathetic activity and decline in parasympathetic tone occurs; the consequent rise in BP and HR during arousals and awakenings significantly exceeds baseline wakefulness levels 17 .
SLEEP-RELATED BREATHING DISORDERS AND HYPERTENSIONOSA is the most common sleep-related breathing disorder, characterized by repeated complete (apnea) or partial (hypopnea) upper airway inspiratory closure in sleep 18 . The severity of OSA is gauged by the number of disordered breathing events per hour of sleep or recording time on a sleep study (in-laboratory polysomnography or a home sleep apnea test). The events are accompanied by oxyhemoglobin desaturation and sometimes with arousals from sleep. Up to 24% of men and 9% of women between 30-60 years of age are estimated to have OSA in the general U.S. adult population, with some other cohorts showing higher prevalence rates of sleep disordered breathing (SDB) (e.g. 50% of men and 23% of women with moderate to severe SDB in a population-based study in Switzerland) 1, 2 .
Mechanisms linking sleep apnea and hypertensionThe chemoreflexes-Whereas in normal sleep, changes in BP are mainly sleep stage dependent, in subjects with SDB, these changes depend on the severity of disordered breathing events 19,20 . Recurrent episodes of cessation of breathing due to upper airway closure or narrowing with accompanying hypoxemia lead to chemoreflex-mediated sympathetic activation 21 . At the termination of the disordered breathing event, an increase in cardiac output occurs, but this is delivered into a constricted vasculature. As a result, intermittent rises in BP as high as 250/110 mm Hg may be noted in individuals with OSA, t...