Sympathetic over activity in the etiology of hypertension of obstructive sleep apnea.

ABSTRACT

Beginning with modest clinical observations in 1984, a picture has evolved suggesting that sympathetic nervous system over activity may be responsible in part for the elevated blood pressure seen in obstructive sleep apnea patients. Early studies of urinary and plasma catecholamines indirectly suggested sympathetic over activity carried to daytime, non-apneic conditions. Later intra-neuronal recordings of muscle sympathetic nerve activity directly demonstrated both acute and diumal (non-apneic) sympathetic over activity. Most importantly, diurnal sympathetic over activity has been shown to diminish with adequate treatment of apnea using nasal CPAP. Norepinephrine and angiotensin II are both released with increased peripheral sympathetic activity and are parallel vascular growth-promoting factors. Thus, one would expect alterations in vascular structure and function in a state of chronic sympathetic over activity. While changes in peripheral vascular structure have not been demonstrated in hypertension of sleep apnea, changes in peripheral vascular responsiveness have. There is reduced response to acetylcholine and isoproterenol vasodilation, and to norepinephrine and angiotensin vasoconstriction in humans with sleep apnea. Some of these vascular reactivity changes are shown to reversed with chronic nasal CPAP treatment. Finally, complimentary to the above evidence in humans, there is indirect evidence of sympathetic over activity as well as differences in vascular reactivity in intermittent hypoxia challenged rats. We have made significant strides in the past 15-20 years towards understanding systemic hypertension related to sleep apnea, especially the role of the sympathetic nervous system. Future research will need to look at exact mechanism of sympathetic nervous system over activity, particularly how central nervous system pathways may undergo facilitation, leading to daytime over activity. Furthermore, the mechanisms of sustained hypertension in sleep apnea patients is almost certainly of multiple etiologies. There is no marker for separating sleep apnea patients with hypertension derived solely from intermittent hypoxia from other secondary causes. Perhaps endothelial cell molecular markers could help to identify patients at risk for cardiovascular change associated with snoring and apnea, as well to guide treatment. Finally, studies demonstrating microvascular changes in blood vessels are extremely difficult to do, but promise to yield important knowledge about cellular mechanisms and results of long-term treatment of sleep apnea on cardiovascular disease.