Endothelin contributes to the blood pressure rise triggered by hypoxia in severe obstructive sleep apnea.

Abstract

Obstructive sleep apnea (OSA) is strongly correlated with an increased risk of systemic hypertension. However, the link between systemic hypertension and nocturnal apneas remains incompletely understood. Animal studies suggest an implication of the endothelin system. The aim of the present study is to determine if endogenous endothelin plays a role in the increase in blood pressure observed during hypoxic episodes in OSA patients, in addition to peripheral chemoreflex and neural sympathetic activation. We assessed the effects of the nonspecific endothelin antagonist bosentan (500 mg; Tracleer; Actelion; Basel, Switzerland) on ventilation, hemodynamics, and muscle sympathetic nerve activity (MSNA) during normoxia and isocapnic hypoxia using a randomized, crossover, double-blinded, placebo-controlled study design, and in 13 severely untreated sleep apneic patients (age 50 ± 9 years, apnea-hypopnea index 35 ± 21/h). Hypoxia increased blood pressure, MSNA, and minute ventilation as oxygen saturation decreased. Bosentan suppressed completely the increase in SBP during a 5-min hypoxic challenge (143 ± 5 mmHg during hypoxia vs. 133 ± 5 mmHg during normoxia with placebo and 127 ± 3 mmHg during hypoxia vs. 125 ± 3 mmHg during normoxia under bosentan, P = 0.023). DBP as well as the rise in MSNA and ventilation during isocapnic hypoxia did not differ between bosentan and placebo. Endothelin contributes to the rise in SBP in response to acute hypoxia in patients with severely untreated OSA. This was not due to lower chemoreflex activation with bosentan.