Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure - Ip et al. (2000)
Nitric oxide (NO) is reduced in patients with obstructive sleep apnea (OSA)
One night of nasal continuous positive airway pressure restores NO concentrations to normal values
Breathing nasally at night might improve NO status, especially in those suffering from OSA
The Breathing Diabetic Summary
Nitric oxide (NO) seems to show up everywhere. I guess that shouldn’t surprise us since NO is a potent vasodilator that plays a key role in oxygenating the entire body. Previously, we learned that obstructive sleep apnea (OSA) causes hypertension, which then has many negative side effects. The authors of this paper hypothesized that NO is playing an important role in causing hypertension associated with OSA. So, they set out to examine how NO is affected by OSA and how nasal continuous positive airway pressure (nCPAP) might help improve NO status in people who suffer from OSA.
They recruited 30 participants with OSA and 40 healthy control subjects. After a night of sleep, they took serum samples of nitrites/nitrates, which are representative of overall NO blood concentration. They found that the NO concentrations of OSA patients were significantly lower than those of the control subjects. A statistical analysis revealed that NO concentrations were negatively correlated with indices of sleep apnea and systolic blood pressure, meaning that as sleep apnea increased, NO decreased, and as blood pressure increased, NO decreased.
They then had 19 of the OSA subjects sleep with an nCPAP machine. The nCPAP device provides positive airflow through the nasal passages throughout the night to prevent airway collapse, thus reducing sleep apnea events. They found that NO concentrations increased significantly after 1 night of nCPAP treatment. In fact, the NO concentrations of the OSA patients were similar to those of the control subjects after just one night of nCPAP therapy.
The authors did not provide a direct mechanism for how nCPAP increased NO so much. But we can speculate. (This is now my opinion, not that of the authors.) We know from previous studies that inhaled NO can have positive impacts throughout the whole body. Moreover, a 2015 PNAS study showed that NO travels throughout the body on the hemoglobin, where it facilitates the oxygenation of the entire body. Finally, we also know that the nasal cavity is warehouse for NO. All together, these results suggest that the nCPAP machine might be restoring NO concentrations to normal simply by encouraging the patients to breathe nasally during sleep.
For us, this study provides more evidence that we should be practicing Principle 2 and taping our mouths at night. Not only will we be breathing naturally during sleep, reducing our risk of sleep apnea, and reducing our risk of hypertension, but we now know that we will likely be increasing our circulating concentrations of nitric oxide and improving oxygenation throughout our entire body.
Abstract from Paper
Epidemiological studies have implicated obstructive sleep apnea (OSA) as an independent comorbid factor in cardiovascular and cerebrovascular diseases. The recurrent episodes of occlusion of upper airways during sleep result in pathophysiological changes that may predispose to vascular diseases, and we postulate that nitric oxide may be one of the mediators involved. This study investigates the levels of circulating nitric oxide (NO), measured as serum nitrites and nitrates, in the early morning in OSA subjects compared with control subjects, and the effect of overnight nasal continuous positive airway pressure (nCPAP) in OSA subjects. Thirty men with moderate to severe OSA (age = 41.9 +/- 9.0; apnea-hypopnea index, AHI = 48.0 +/- 18.1) were compared with 40 healthy men (age = 40.6 +/- 5.4; AHI = 1.4 +/- 1.2). Serum nitrite/nitrate levels were significantly lower in OSA subjects (OSA = 38.9 +/- 22.9 microM, control subjects = 63.1 +/- 47.5 microM, p = 0.015). There was significant negative correlation between serum nitrites/nitrates and the following parameters: AHI (r = -0.389, p = 0.001), oxygen desaturation time (r = -0.346, p = 0.004), and systolic blood pressure (BP) (r = -0.335, p = 0.005). Stepwise multiple linear regression with systolic or diastolic BP as the dependent variable identified serum nitrites/nitrates as the only significant correlate. Twenty-two OSA subjects had measurements of serum NO at baseline and after an overnight application nCPAP. There was significant increase in serum NO after nCPAP (baseline = 30.5 +/- 14.4 microM, after nCPAP = 81.0 +/- 82.1 microM, p = 0.01). This study demonstrates, for the first time, that circulating NO is suppressed in OSA, and this is promptly reversible with the use of nCPAP. The findings offer support for nitric oxide being one of the mediators involved in the acute hemodynamic regulation and long-term vascular remodeling in OSA.
Ip MS1, Lam B, Chan LY, Zheng L, Tsang KW, Fung PC, and Lam WK, (2000) Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure, American Journal of Respiratory and Critical Care Medicine, 162 (6), 2166 – 2171.