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The effects of hypoxia and sleep apnea on isoproterenol sensitivity
P J Mills1, J E Dimsdale, S Ancoli-Israel
1Department of Psychiatry, UCSD Medical Center, University of California, San Diego 92103-0804, USA. pmills@ucsd.edu
Study Objectives:
To determine the effects of both apnea and hypoxia on beta-adrenergic receptor sensitivity.
Design:
Cross-sectional study.
Setting:
A clinical research center.
Patients:
Forty-five normotensive and hypertensive sleep apnea patients (respiratory disturbance index >20) and non-apneic controls.
Measurements And Results:
The chronotropic 25 dose (CD25), an in vivo measure of beta-adrenergic receptor sensitivity derived from the heart rate response to a graded infusion of isoproterenol, was determined while subjects breathed either a normoxic (21% O2, 79% N2) or a hypoxic (15% O2, 85% N2) gas mixture. Under normoxic conditions, apnea patients showed a significantly higher CD25 (lower beta-adrenergic receptor sensitivity) as compared to controls (5.9 microg, SD=2.1 versus 4.6 microg, SD=1.2, respectively; p=0.018). In response to hypoxia, apnea patients showed no change in CD25, while controls showed a significant increase in CD25 (beta-adrenergic receptor desensitization) (p=0.002), to a value comparable to the apneics' (5.6 microg, SD=2.0).
Conclusion:
The in vivo finding of reduced beta-adrenergic receptor sensitivity in sleep apnea patients is consistent with previous in vitro assessments of the beta-adrenergic receptor. The finding that apnea patients do not respond to hypoxia with a further receptor desensitization suggests that sleep apnea patients may have reached a threshold effect of hypoxia on the beta-adrenergic receptor. These findings may be relevant to the greater incidence of hypertension seen in patients with sleep apnea syndrome.