Am. J. Respir. Crit. Care Med., Volume 162, Number 4, October 2000, 1480-1487

Reduced - and ₂-Adrenergic Vascular Response in Patients with Obstructive Sleep Apnea

LUDGER GROTE, HOLGER KRAICZI, and JAN HEDNER

Department of Clinical Pharmacology and Sleep Laboratory, Sahlgrenska University Hospital, Göteborg, Sweden

Obstructive sleep apnea (OSA) has been associated with increased sympathetic activity. This study tested the hypothesis that the - and 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 µg/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 - and -receptor stimulation suggests a functional downregulation of vascular sympathoadrenergic receptors in patients with sleep apnea.

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