interleukin-8 and Sleep-Apnea-Syndromes

Patient data report marked gender and pre-vs-postmenopausal differences in obstructive sleep apnea (OSA). However, no experimental data are available on how sexual hormones modulate OSA consequences. Here we report novel results on estrogen-modulated heart and brain inflammation in female mice subjected to intermittent hypoxia, a major injurious challenge in OSA. C57BL/6J (14-week old) intact and ovariectomized mice (n=6 each) were subjected to intermittent hypoxia (20 s at 5% and 40s at 21%, 60 cycles/h; 6 h/day). Identical intact and ovariectomized groups breathing room air were controls. After 30 days, the gene expressions of interleukins 6 and 8 (IL-6, IL-8) in the brain and heart tissues were measured. Whereas, compared with normoxia, intermittent hypoxia considerably increased IL-6 and IL-8 gene expressions in intact females, no change was found in ovariectomized mice when comparing normoxia and intermittent hypoxia. These data suggest that estrogens modulate the inflammatory effects of intermittent hypoxia and point to further studies on the role played by sex hormones in OSA.

Topics: Animals; Brain; Disease Models, Animal; Encephalitis; Female; Gene Expression Regulation; Heart Injuries; Hypoxia; Interleukin-6; Interleukin-8; Mice; Mice, Inbred C57BL; Myocardium; Organ Size; Ovariectomy; RNA, Messenger; Sleep Apnea Syndromes; Time Factors

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.

Topics: Adiponectin; Adult; Blood Pressure; Body Mass Index; C-Reactive Protein; Chemokine CCL5; Female; Humans; Hypertension; Hypoxia; Intercellular Adhesion Molecule-1; Interleukin-8; Leptin; Male; Receptors, Interleukin-1; Sleep Apnea Syndromes; Sympathetic Nervous System; Tumor Necrosis Factor-alpha