allopurinol and Sleep-Apnea-Syndromes

Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction. The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea. A randomised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea, comparing 300 mg allopurinol daily for 2 weeks with placebo. Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation (FMD) at baseline and following treatment. Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress. Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of <90%. Allopurinol caused a significant increase in FMD compared to placebo (10.4+/-3.2 versus 7.4+/-2.8%, respectively). Plasma malondialdehyde levels were significantly reduced with allopurinol treatment (1.5+/-0.3 versus 1.2+/-0.3 micromol.L(-1)), consistent with reduced oxidative stress. Allopurinol improves endothelial dysfunction in patients with moderate-to-severe obstructive sleep apnoea. These observations suggest that xanthine oxidase contributes significantly to vasodilatory impairment.

Topics: Adult; Allopurinol; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Sleep Apnea Syndromes

Based on the fact that erythropoietin (Epo) administration in rodents protects against spatial learning and cognitive deficits induced by chronic intermittent hypoxia (CIH)-mediated oxidative damage, here we tested the hypothesis that Epo in the brain protects against cardiorespiratory disorders and oxidative stress induced by CIH in adult mice.. Adult control and transgenic mice overexpressing Epo in the brain only (Tg21) were exposed to CIH (21%-10% O2-10 cycles/hour-8 hours/day-7 days) or room air. After CIH exposure, we used the tail cuff method to measure arterial pressure, and whole-body plethysmography to assess the frequency of apneic episodes at rest, minute ventilation, and ventilatory responses to hypoxia and hypercapnia. Finally, the activity of pro-oxidant (XO-xanthine oxidase, and NADPH) and antioxidant (super oxide dismutase) enzymes was evaluated in the cerebral cortex and brainstem.. Exposure of control mice to CIH significantly increased the heart rate and arterial pressure, the number of apneic events, and the ventilatory response to hypoxia and hypercapnia. Furthermore, CIH increased the ratio of pro-oxidant to antioxidant enzymes in cortex and brainstem tissues. Both physiological and molecular changes induced by CIH were prevented in transgenic Tg21 mice.. We conclude that the neuroprotective effect of Epo prevents oxidative damage in the brain and cardiorespiratory disorders induced by CIH. Considering that Epo is used in clinics to treat chronic kidney disease and stroke, our data show convincing evidence suggesting that Epo may be a promising alternative drug to treat sleep-disorder breathing.

Topics: Animals; Apnea; Arterial Pressure; Brain; Brain Stem; Cerebral Cortex; Erythropoietin; Heart Rate; Hypercapnia; Hypoxia; Male; Mice; Mice, Transgenic; NADP; Oxidative Stress; Plethysmography, Whole Body; Pulmonary Ventilation; Reactive Oxygen Species; Rest; Sleep Apnea Syndromes; Superoxide Dismutase; Xanthine Oxidase

We tested the hypothesis that estradiol (E2) protects against cardiorespiratory disorders and oxidative stress induced by chronic intermittent hypoxia (CIH) in adult female rats.. Sprague-Dawley female rats (230-250 g) were ovariectomized and implanted with osmotic pumps delivering vehicle or E2 (0.5 mg/kg/d). After 14 days of recovery, the rats were exposed to CIH (21%-10% O2: 8 h/d, 10 cycles per hour) or room air (RA). After 7 days of CIH or RA exposure, we measured arterial pressures (tail cuff), metabolic rate (indirect calorimetry), minute ventilation, the frequency of sighs and apneas at rest, and ventilatory responses to hypoxia and hypercapnia (whole body plethysmography). We collected the cerebral cortex, brainstem, and adrenal glands to measure the activity of NADPH and xanthine oxidase (pro-oxidant enzymes), glutathione peroxidase, and the mitochondrial and cytosolic superoxide dismutase (antioxidant enzymes) and measured lipid peroxidation and advanced oxidation protein products (markers of oxidative stress).. CIH increased arterial pressure, the frequency of apnea at rest, and the hypoxic and hypercapnic ventilatory responses and reduced metabolic rate. CIH also increased oxidant enzyme activities and decreased antioxidant activity in the cortex. E2 treatment reduced body weight and prevented the effects of CIH.. E2 prevents cardiorespiratory disorders and oxidative stress induced by CIH. These observations may help to better understand the underlying mechanisms linking menopause and occurrence of sleep apnea in women and highlight a potential advantage of hormone therapy.

Topics: Animals; Antioxidants; Blood Pressure; Body Weight; Estradiol; Female; Glutathione Peroxidase; Heart; Hypercapnia; Hypoxia; NADP; Oxidative Stress; Rats; Rats, Sprague-Dawley; Respiration; Rest; Sleep Apnea Syndromes; Superoxide Dismutase; Xanthine Oxidase

Topics: Adult; Age Factors; Allopurinol; Body Mass Index; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Sex Factors; Sleep Apnea Syndromes; Vasodilation; Xanthine Oxidase