Sleep apnea, norepinephrine-release rate, and daytime hypertension
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Updated: Nov 1, 2026

A Model to Simulate Clinically Relevant Hypoxia in Humans
Published on: December 22, 2016
M G Ziegler1, R Nelesen, P Mills
1Department of Medicine, University of California-San Diego School of Medicine, USA.
Abstract:
Patients with obstructive sleep apnea (OSA) are often hypertensive, and both apneics and hypertensives are reported to have increased sympathetic nerve activity. We measured plasma norepinephrine (NE) levels, clearance, and release rate among 65 subjects who breathed room air, a hypoxic gas mixture, and the hypoxic mixture combined with intermittent breath holding. Apneics' plasma NE across all three breathing conditions was 307 pg/ml compared with the non-apneics' level of 248 pg/ml (p = 0.017). NE clearance increased from 3.2 l/minute to 3.9 l/minute when subjects breathed a hypoxic gas mixture (p < 0.001). NE clearance was similar among normal controls, apneics, and hypertensives. The rate at which NE was released from sympathetic nerves into the bloodstream was higher among hypertensives but not among apneics while subjects breathed room air. Hypoxia increased the NE-release rate from 892 ng/minute to 1,042 ng/minute (p < 0.001) and increased the NE-release rate more among apneics than non-apneics (p < 0.001). The NE-release rate response to hypoxia and breath holding differed between hypertensives and normotensives (p < 0.001) and between apneics and non-apneics (p < 0.001). Normotensive apneics had the largest increase in NE release during hypoxia. Like other investigators, we found that plasma NE levels were increased among apneics. Calculation of NE-release rate and correction for blood pressure status revealed a more complex situation. Apneics breathing room air had a normal NE-release rate; any increase in sympathetic neuronal NE release could be attributed to apneics who were also hypertensive. However, apneics had a greater NE response to hypoxia. These results suggest that apneics are susceptible to transient increases in sympathetic nervous activity and that hypertensive apneics maintain increased sympathetic nervous release of NE in the daytime.
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