Reduced alpha- and beta(2)-adrenergic vascular response in patients with obstructive sleep apnea.
Obstructive sleep apnea (OSA) has been associated with increased sympathetic activity. This study tested the hypothesis that the alpha- and beta(2)-receptor-mediated vascular response is altered in patients with OSA. Forearm vascular resistance was evaluated by venous occlusion plethysmography in 10 normotensive OSA patients and 10 normotensive controls (apnea/hypopnea index [mean +/- SD] 29.4 +/- 2.3 and 1.6 +/- 0.3 per hour, respectively) roughly matched for body mass index (BMI) and age. Forearm vascular resistance was measured after intraarterial infusion of norepinephrine (NE) (7.4, 31, 120, 472 and 1421 pmol/100 ml forearm volume [FAV]/min), before and after phentolamine infusion (2 microgram/100 ml FAV/min), and isoproterenol (ISO) (1, 2, 6, and 15 ng/100 ml FAV/min). NE-induced vasoconstriction was significantly attenuated in OSA patients compared with controls (65.0 +/- 36.6% versus 129.4 +/- 81.8%, p = 0.049). The reduction of vascular resistance after phentolamine was similar in patients and control subjects (-50.8 +/- 16.7% versus -43.4 +/- 20.0%, p = 0.38). During ongoing phentolamine infusion NE increased resistance to a similar extent in both groups (0.5 +/- 4.9% versus -0.9 +/- 10.1%, p = 0.96). Vasodilation following ISO was significantly attenuated in OSA patients compared with control subjects (-53.3 +/- 9.0% versus -64.7 +/- 10.3%, p = 0.049). Moreover, the vascular response to NE in OSA patients was negatively correlated with plasma NE concentration (r = -0.76, p < 0.05). The reduced vascular response to alpha- and beta-receptor stimulation suggests a functional downregulation of vascular sympathoadrenergic receptors in patients with sleep apnea.
Grote
L
L
Department of Clinical Pharmacology and Sleep Laboratory, Sahlgrenska University Hospital, Göteborg, Sweden. ludger.grote@pharm.gu.se
Kraiczi
H
H
Hedner
J
J
D000328:Adult; D001783:Blood Flow Velocity / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D012891:Sleep Apnea Syndromes / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014655:Vascular Resistance / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D018343:Receptors, Adrenergic, beta-2