In North America as many as 24 percent of adults suffer from sleep-disordered breathing, a problem exacerbated by obesity. People with obstructive sleep apnea cease breathing for about 15 seconds, every few minutes, hundreds of times a night. Besides feeling drowsy and exhausted the next day, people with sleep apnea face high blood pressure and risk heart attacks and stroke. Indeed, they are about three times as likely to die from a heart attack in the middle of the night as the general population, according to a study in the March 24 New England Journal of Medicine. "The consequences of this intermittent [oxygen deprivation], if it persists for years, can be very drastic," says physiologist Nanduri R. Prabhakar of Case Western Reserve University.
Prabhakar has long been mystified by sleep apnea: Why does a brief shutdown of oxygen intake spark an extreme cardiovascular response? After all, people living at high altitude--for example, in the Andes--adapt perfectly well to a low-oxygen environment without developing hypertension.
To pursue this question in molecular detail, he re-created sleep apnea in rats by cutting the oxygen to their cages with a frequency similar to that experienced by human sufferers. At the same time, other rats breathed continuously in a low-oxygen atmosphere that replicated conditions in mountainous areas. Within 10 days, only the rats exposed to oxygen in fits and starts developed hypertension. The most dramatic difference between both groups, Prabhakar announced at a Novartis Foundation meeting in London this past January, showed up in the carotid body, an oxygen-sensing tissue located in the main artery in the neck.
Normally, when oxygen levels drop, the carotid body tells the nervous system that blood pressure must rise to deliver more oxygen to compensate for the shortfall. These urgent signals are prompted by oxygen free radicals acting as messengers. But when oxygen levels plummet repeatedly, as they do in sleep apnea, free radicals overwhelm the carotid body. The excess jams the carotid body into the "on" mode, so that even when oxygen levels return to normal, blood pressure continues to surge.
Prabhakar speculates that free radical scavengers might counter the devastating effects of sleep apnea. He has tested one such compound--a superoxide dismutase mimetic--in his rat model and found that the chemical averted hypertension. Could a humble antioxidant vitamin supplement do the same for human patients? An antioxidant pill would be an ideal solution, because the only existing therapy is cumbersome: it involves wearing a face mask connected to a positive airway pressure machine during the night to maintain a constant oxygen level.
"Sleep apnea is a much neglected problem," says Prabhakar, whose findings have enhanced our knowledge about the perils that lurk behind these broken nights. He hopes human trials of antioxidant therapy will be able to start soon.