The effects of hypoxia and sleep apnea on isoproterenol sensitivity

Study Objectives: To determine the effects of both apnea and hypoxia on a-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 nonapneic 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% O-2, 79% N-2) Or a hypoxic (15% O-2, 85% N-2) gas mixture. Under normoxic conditions, apnea patients showed a significantly higher CD25 (lower beta-adrenergic receptor sensitivity) as compared to controls (5.9 mu g, SD=2.1 versus 4.6 mu g, 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 mu g, 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.