199Sympathetic Activation and Intermittent Hypoxia
Sympathetic activation is a key mechanism responsible for the resistant hyperten-
sion seen in patients with OSA. Several studies have demonstrated deranged auto-
nomic function during both the night and day in patients with OSA, suggesting that
the hypertension observed at night has a carryover effect that extends into the day-
time hours and persists over time. The repetitive cessation of airflow during apneic
and hypopneic episodes leads to recurrent hypoxemia and hypercapnia. This trig-
gers chemoflex activation, resulting in stimulation of sympathetic activity. Studies
of healthy human subjects have shown that periods of intermittent hypoxemia
resulted in elevations in blood pressure and sympathetic activation [ 36 , 37 ] that
decreased with resumption of ventilation after apneic episodes. Interestingly, the
frequency of hypoxic episodes, captured as an oxygen desaturation index, appears
to be more important that the AHI in predicting the odds of OSA-related prevalent
hypertension [ 38 ].
Activated Renin-Angiotensin-Aldosterone System
Aldosterone excess has also been hypothesized to play a role in the relationship
between OSA and hypertension. Plasma aldosterone levels have been found to cor-
relate strongly and significantly with AHI, a relationship seen in subjects with resis-
tant hypertension but not in normotensive controls [ 29 ]. In support of the concept that
fluid accumulation may worsen OSA, one study showed that drug-resistant hyperten-
sive patients exhibited a great shift in the volume of fluid that migrated rostrally from
the legs overnight and had a correspondingly higher AHI, than patients whose hyper-
tension was well controlled [ 39 ]. A small but provocative study also suggested that
anti-aldosteronic diuretics may reduce parapharyngeal edema and secondary upper
airway obstruction, thereby improving both OSA severity and BP [ 40 ]. These data
support the possibility of a bidirectional relationship between OSA and hypertension,
whereby treatment of hypertension may improve OSA severity.
Inflammation and Oxidative Stress
The repeated cycles of deoxygenation and subsequent reoxygenation seen in OSA
are associated with generation of reactive oxygen species and oxidative stress, with
increases in levels of circulating adhesion molecules and inflammatory cytokines
including TNF-alpha and IL-8.
13 Obstructive Sleep Apnea and Resistant Hypertension