14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans

Abstract

Obstructive sleep apnoea syndrome (OSAS) causes nocturnal chronic intermittent hypoxia (IH) that contributes to excess cardiovascular morbidity. To explore the consequences of IH, we used our recently developed model of nocturnal IH in healthy humans to characterise the profile of this blood pressure increase, to determine if it is sustained and to explore potential physiological mechanisms.We performed 24-h ambulatory monitoring of blood pressure in 12 healthy subjects before and after 2 weeks of IH exposure. We also assessed systemic haemodynamics, muscle sympathetic nerve activity (MSNA), ischaemic calf blood flow responses and baroreflex gain. We obtained blood samples for inflammatory markers before, during and after exposure. IH significantly increased daytime ambulatory blood pressure after a single night of exposure (3 mmHg for mean and diastolic) and further increased daytime pressures after 2 weeks of exposure (8 mmHg systolic and 5 mmHg diastolic). Mean¡SD MSNA increased across the exposure (17.2¡5.1 versus 21.7¡7.3 bursts?min -1 ; p,0.01) and baroreflex control of sympathetic outflow declined from -965.3¡375.1 to -598.4¡162.6 AIU?min -1 ?mmHg -1 (p,0.01). There were no evident changes in either vascular reactivity or systemic inflammatory markers. These data are the first to show that the arterial pressure rise is sustained throughout the waking hours beyond the acute phase immediately after exposure. Moreover, they may suggest that sympathoactivation induced by IH likely contributes to blood pressure elevation and may derive from reduced baroreflex inhibition. These mechanisms may reflect those underlying the blood pressure elevation associated with OSAS.

Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia‐Induced Vascular Alterations

“…Our data are consistent with the literature, which reports the following: (1) an independent association between OSA and hypertension in humans34 and (2) a determinant role of chronic IH in inducing elevation of arterial and blood pressure in healthy humans and animals exposed to IH 35, 36, 37. We further demonstrated that, in addition to the elevation of arterial blood pressure, IH also induces an arterial inflammatory remodeling with subsequent stiffening.…”

Low Physical Activity Is a Determinant for Elevated Blood Pressure in High Cardiovascular Risk Obstructive Sleep Apnea

“…1,2 The repetitive occurrence of apneas and hypopneas with the associated intermittent hypoxia sequence causes acute surges in blood pressure (BP), sleep fragmentation, and chronic sympathetic activation that ul-timately lead to sustained hypertension. 3 A large body of evidence from animal models, intermittent hypoxia exposure of healthy humans 4 and epidemiological studies support an independent role of OSA in the pathogenesis of daytime hypertension. 2,5,6 However, it has been shown that CPAP, the first line therapy for OSA, has a limited effect on blood pressure control, 7,8 and the size of the effect is highly related to the duration of nightly CPAP usage.…”

Obstructive Sleep Apnoea Syndrome as a Systemic Low-Grade Inflammatory Disorder

“…In a recent study in healthy humans, IH significantly increased sympathetic activity and daytime blood pressure after a single night of exposure. The baroreflex control of sympathetic outflow declined (Tamisier et al, 2011). Surges in sympathetic nervous system activity associated with apneic events have also been related to antifibrinolytic activity reflected by elevations in PAI-1 (von & Dimsdale, 2003).…”