Obstructive sleep apnea as a cause of systemic hypertension: Evidence from a canine model - Brooks et al. (1997)

Key Points

  • Obstructive sleep apnea (OSA) causes hypertension and is related to sleep-disordered breathing, not sleep fragmentation

  • OSA-caused hypertension is quickly reversible when OSA is treated

The Breathing Diabetic Summary

Obstructive sleep apnea (OSA) is associated with many negative cardiovascular outcomes.  One of the most common is hypertension.  However, when this paper was published, a direct cause-and-effect relationship had not been established between OSA and hypertension.  Therefore, this study set out to see if OSA caused hypertension, or if the two were simply associated.

(Side Note/Disclaimer: This study used dogs a subjects and essentially forced OSA on them.  I have two dogs, and I consider them children.  Thus, I was very conflicted reading this paper.  However, as far as I can tell, the dogs went back to normal after completion of the study.)

With that said, let’s look at their protocol.  The study had 4 dogs and used a device to mimic OSA.  They progressively increased the severity of the OSA events throughout the duration of the study to closely mimic human cases.  They studied the dogs in a 1-2 month period leading up to the experiment, for 1-3 months of OSA, and for 1 month after cessation of the OSA trial. 

Then, 6 months later, the same dogs were studied again to look at the effects of arousal from sleep versus OSA.  Basically, the authors wanted to see if OSA was causing hypertension by constant arousals from sleep, or if it was related to the disrupted breathing itself.  In this trial, the dogs were woken up frequently throughout the night with a loud noise.

They found that OSA caused systemic hypertension, during both day and night.  Mean arterial blood pressure increased greater than 10 mmHg during both these periods due to OSA.  Remarkably, the dogs’ nighttime blood pressure returned to normal immediately after stopping OSA, indicating that the hypertension is reversible.  Daytime hypertension slowly went away over a 1-3 week period after OSA ceased.

When the dogs were subjected to sleep fragmentation without OSA, their nighttime blood pressure rose to levels similar to those caused by OSA.  However, their daytime blood pressure remained nearly constant.  So, OSA caused both daytime and nighttime hypertension whereas sleep arousal only caused hypertension during the night.  It’s as if the stress of being constantly woken up raised their blood pressure acutely, but then went away once the dogs were “fully” awake.

Because sleep fragmentation did not have the same effects as OSA, the authors suspect that OSA causes hypertension through frequent periods of hypoxia and fluctuations in thoracic pressure.  However, we also know from two studies published in 2000 (here & here) that OSA decreases circulating nitric oxide, which might also be playing a role here.

Overall, although this study was rather sad, it showed that OSA causes hypertension. As diabetics who suffer from higher incidences of both OSA and hypertension, these results are especially important for us. However, there is practical way forward. Because nasal breathing at night can reduce OSA, and slow breathing during the day can reduce hypertension, the use of Principle 1 and Principle 2 has the potential to prevent and treat the negative side effects of OSA.

Abstract from Paper

Several epidemiological studies have identified obstructive sleep apnea (OSA) as a risk factor for systemic hypertension, but a direct etiologic link between the two disorders has not been established definitively. Furthermore, the specific physiological mechanisms underlying the association between OSA and systemic hypertension have not been identified. The purpose of this study was to systematically examine the effects of OSA on daytime and nighttime blood pressure (BP). We induced OSA in four dogs by intermittent airway occlusion during nocturnal sleep. Daytime and nighttime BP were measured before, during, and after a 1-3-mo long period of OSA. OSA resulted in acute transient increases in nighttime BP to a maximum of 13.0+/-2.0 mmHg (mean+/-SEM), and eventually produced sustained daytime hypertension to a maximum of 15.7+/-4.3 mmHg. In a subsequent protocol, recurrent arousal from sleep without airway occlusion did not result in daytime hypertension. The demonstration that OSA can lead to the development of sustained hypertension has considerable importance, given the high prevalence of both disorders in the population.

Journal Reference:

Dina Brooks, Richard L. Horner, Louise F. Kozar, Caroline L. Render-Teixeira, and Eliot A. Phillipson, (1997) Obstructive sleep apnea as a cause of systemic hypertension: Evidence from a canine model, The Journal of Clinical Investigation, 99 (1), 106 – 109, doi: 10.1172/JCI119120.