The effects of hypoxia and sleep apnea on isoproterenol sensitivity

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.