Effects of obstructive sleep apnea on endothelin-1 and... : Journal of Hypertension (original) (raw)

Original article

Phillips, Bradley G.1; Narkiewicz, Krzysztof2; Pesek, Catherine A.2; Haynes, William G.2; Dyken, Mark E.3; Somers, Virend K.2,4

1Division of Clinical and Administrative Pharmacy, University of Iowa College of Pharmacy, Iowa City, USA

2Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA

3Sleep Laboratory, Department of Neurology, University of Iowa College of Medicine, Iowa City, USA.

4Correspondence and requests for reprints to Dr Virend K. Somers, University of Iowa College of Medicine, Department of Internal Medicine, Cardiovascular Center, 200 Hawkins Drive, Iowa City, IA 52242, USA. Tel: +1 319 353 6576; fax: +1 319 353 6343; E-mail: [email protected].

Sponsorship: These studies were supported by an American Heart Association Established Investigator Grant, an NIH Sleep Academic Award, NIH/HL14388 (V.K.S.), and an American College of Clinical Pharmacy/Rhone–Poulenc Rorer Cardiovascular Research Award (B.G.P.).

Received 2 February 1998 Revised 18 September 1998 Accepted 22 September 1998

Abstract

Objective

To evaluate blood pressure and humoral vasoconstrictor responses to recurrent episodes of obstructive sleep apnea and the effects of therapy by means of continuous positive airway pressure.

Patients and methods

We prospectively evaluated overnight changes in hemodynamics, oxygen saturation, the apnea–hypopnea index, circulating endothelin-1, norepinephrine and plasma renin activity in 22 patients with severe obstructive sleep apnea before and after successful therapy using continuous positive airway pressure therapy (three measurements). Measurements of endothelin-1 and blood pressure were also obtained on three occasions, at similar times, in 12 healthy control subjects without sleep disturbances.

Results

Mean arterial pressure and endothelin-1 concentrations increased significantly after 4 h of untreated obstructive sleep apnea, and decreased after 5 h of continuous positive airway pressure. Changes in endothelin-1 levels were correlated with changes in mean arterial pressure (r = 0.44, P < 0.02) and with changes in oxygen saturation (r = 0.37, P < 0.05). Norepinephrine levels and plasma renin activity did not change significantly in patients with obstructive sleep apnea, and were not correlated with changes in blood pressure or oxygen saturation. In controls, blood pressure measurements at similar times during the night showed changes directionally opposite to that seen in obstructive sleep apnea, while endothelin-1 levels remained unchanged.

Conclusions

Sleep apnea elicits increases in blood pressure and endothelin-1, with reductions in both after treatment. Vasoconstrictor and mitogenic effects of endothelin-1 may be implicated in increased cardiovascular risk in patients with obstructive sleep apnea.