Intermittent Hypoxia Induces Early Functional Cardiovascular Remodeling in Mice

Demattéis, Maurice; Julien, Cécile; Guillermet, Christiane; Stürm, Nathalie; Lantuéjoul, Sylvie; Mallaret, Michel; Lévy, Patrick; Gozal, Evelyne

doi:10.1164/rccm.200702-238oc

Cited by 146 publications

(145 citation statements)

References 31 publications

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“…However, there is good evidence that equivalence exists between the two measures of OSAS severity [49], and indeed ODI is at least as reproducible as the AHI between repeated nights [50]. Furthermore, oscillations in oxygen levels may be more pertinent to the vascular effects of OSA than apnoeic events [51] and therefore the current authors believe that the use of an ODI rather than an AHI does not limit the interpretation of their data.…”

Section: Study Limitationsmentioning

confidence: 82%

CPAP and measures of cardiovascular risk in males with OSAS

Kohler¹,

Pepperell²,

Casadei³

et al. 2008

Eur Respir J

175

115

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Obstructive sleep apnoea syndrome (OSAS) has been associated with hypertension, stroke and myocardial ischaemia in epidemiological and observational studies. Continuous positive airway pressure (CPAP) is the treatment of choice for OSAS, but the impact of this intervention on established risk factors for cardiovascular disease remains incompletely understood.A total of 102 males with moderate-to-severe OSAS were randomised to therapeutic (n551) or subtherapeutic (n551) CPAP treatment for 4 weeks to investigate the effects of active treatment on 24-h urinary catecholamine excretion, baroreflex sensitivity (BRS), arterial stiffness (augmentation index) and 24-h ambulatory blood pressure (ABP).After 4 weeks of therapeutic CPAP, significant reductions were seen in urine normetanephrine excretion (from mean¡SD 179.7¡80.1 to 132.7¡46.5 mmol?mol -1 creatinine) and augmentation index (from 14.5¡11.3 to 9.1¡13.8%) compared with the subtherapeutic control group. Furthermore, therapeutic CPAP significantly improved BRS (from 7.1¡3.3 to 8.8¡4.2 ms?mmHg) and reduced mean arterial ABP by 2.6¡5.4 mmHg.In conclusion, treatment of obstructive sleep apnoea with continuous positive airway pressure may lower cardiovascular risk by reducing sympathetic nerve activity, ambulatory blood pressure and arterial stiffness and by increasing sensitivity of the arterial baroreflex.

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Section: Study Limitationsmentioning

confidence: 82%

CPAP and measures of cardiovascular risk in males with OSAS

Kohler¹,

Pepperell²,

Casadei³

et al. 2008

Eur Respir J

175

115

View full text Add to dashboard Cite

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“…An experimental study using mice suggested that chronic intermittent hypoxia itself induces sympathetic hyperactivation, and thus increases HR. 25 Ziegler et al, 23 showed that CPAP treatment for 10 days lowered daytime HR, as well as plasma and urine noradrenaline. In another study, 26 CPAP treatment for 3-4 days also reduced HR in OSA patients.…”

Section: Discussionmentioning

confidence: 99%

Effects of long-term treatment for obstructive sleep apnea on pulse wave velocity

Saito

Sugiyama

et al. 2010

Hypertens Res

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Continuous positive airway pressure (CPAP) treatment improves endothelial function and sympathetic activity in patients with obstructive sleep apnea (OSA). However, the long-term effects of CPAP on pulse wave velocity (PWV), which reflects arterial stiffness that is associated with cardiovascular events, have not been evaluated in OSA patients with or without hypertension (HT). In this study, 212 male OSA patients who had been receiving CPAP treatment for 2 years and were divided into two groups, those with HT (n¼114) and those without (n¼98), were studied. In both HT and normotensive (NT) patients, PWV decreased significantly over the first 6 months of treatment (P¼0.005 and 0.010, respectively), before increasing gradually from 6 to 24 months. Body mass index (BMI), body weight, heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels decreased significantly in the HT group over the 2 years of CPAP treatment (Po0.001 for all). In contrast, only HR decreased significantly in the NT group over the 2 years of treatment (Po0.001). Multivariate regression analysis revealed that age (P¼0.008), decreases in DBP (Po0.001) and HR (Po0.001) and higher initial levels of serum high-density lipoprotein-cholesterol (P¼0.040) were independent factors related to changes in PWV over the 2 years of CPAP treatment in all patients. In conclusion, we found a significant decrease in PWV in both NT and HT patients after 6 months of CPAP treatment. In HT patients, long-term CPAP treatment significantly decreases blood pressure, which may contribute to explain the PWV improvement.

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“…Using animal models 15,24 and also applying IH in healthy humans 25 suggest that IH is a major factor determining blood pressure increase. We have previously shown in C57BL6 mice that blood pressure surges appear at each hypoxic episode, and are associated with increased sympathetic activation 14 . These hemodynamic changes are well known to induce functional and structural alterations of the vascular wall that could contribute to vascular remodeling and atherogenesis 15,26 .…”

Section: Blood Pressure Alterations Due To Ihmentioning

confidence: 93%

“…However, it is well established that atherosclerosis is a chronic inflammatory disease 13 , and there is growing evidence that OSA is a chronic low grade inflammation. Therefore, IH-induced inflammation could be an additional link between OSA and atherosclerosis 9 , without the use of a dyslipidemic diet and even after a short-term of IH exposure, as we previously showed that 14 days of IH were sufficient to induce vascular alterations 14,15 .…”

Section: Introductionmentioning

confidence: 89%