The effects of hypoxia and sleep apnea on isoproterenol sensitivity.
OBJECTIVE
To determine the effects of both apnea and hypoxia on beta-adrenergic receptor sensitivity.


METHODS
Cross-sectional study.


METHODS
A clinical research center.


METHODS
Forty-five normotensive and hypertensive sleep apnea patients (respiratory disturbance index >20) and non-apneic controls.


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).


CONCLUSIONS
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.
Mills
P J
PJ
Department of Psychiatry, UCSD Medical Center, University of California, San Diego 92103-0804, USA. pmills@ucsd.edu
Dimsdale
J E
JE
Ancoli-Israel
S
S
Clausen
J
J
Loredo
J S
JS
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D003430:Cross-Sectional Studies; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis; D000860:Hypoxia / Q000175:diagnosis*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects*; D012891:Sleep Apnea Syndromes / Q000150:complications / Q000175:diagnosis*
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol