title: Intermittent hypoxia and diet-induced obesity: effects on oxidative status, sympathetic tone, plasma glucose and insulin levels, and arterial pressure.
abstract: Obstructive sleep apnea (OSA) consists of sleep-related repetitive obstructions of upper airways that generate episodes of recurrent or intermittent hypoxia (IH). OSA commonly generates cardiovascular and metabolic pathologies defining the obstructive sleep apnea syndrome (OSAS). Literature usually links OSA-associated pathologies to IH episodes that would cause an oxidative status and a carotid body-mediated sympathetic hyperactivity. Because cardiovascular and metabolic pathologies in obese patients and those with OSAS are analogous, we used models (24-wk-old Wistar rats) of IH (applied from weeks 22 to 24) and diet-induced obesity (O; animals fed a high-fat diet from weeks 12 to 24) to define the effect of each individual maneuver and their combination on the oxidative status and sympathetic tone of animals, and to quantify cardiovascular and metabolic parameters and their deviation from normality. We found that IH and O cause an oxidative status (increased lipid peroxides and diminished activities of superoxide dismutases), an inflammatory status (augmented C-reactive protein and nuclear factor kappa-B activation), and sympathetic hyperactivity (augmented plasma and renal artery catecholamine levels and synthesis rate); combined treatments worsened those alterations. IH and O augmented liver lipid content and plasma cholesterol, triglycerides, leptin, glycemia, insulin levels, and HOMA index, and caused hypertension; most of these parameters were aggravated when IH and O were combined. IH diminished ventilatory response to hypoxia, and hypercapnia and O created a restrictive ventilatory pattern; a combination of treatments led to restrictive hypoventilation. Data demonstrate that IH and O cause comparable metabolic and cardiovascular pathologies via misregulation of the redox status and sympathetic hyperactivity.
authors.affiliation: Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine, Vallodolid, Spain; and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Vallodolid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Olea
authors.affiliation: Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine, Vallodolid, Spain; and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Vallodolid, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Agapito
authors.affiliation: Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine, Vallodolid, Spain; and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Vallodolid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallego-Martin
authors.affiliation: Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine, Vallodolid, Spain; and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Vallodolid, Spain.
authors.forename: Asuncion
authors.initials: A
authors.lastname: Rocher
authors.affiliation: Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine, Vallodolid, Spain; and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Vallodolid, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Gomez-Niño
authors.affiliation: Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine, Vallodolid, Spain; and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Vallodolid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Obeso
authors.affiliation: Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine, Vallodolid, Spain; and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Vallodolid, Spain constanc@ibgm.uva.es.
authors.forename: Constancio
authors.initials: C
authors.lastname: Gonzalez
authors.affiliation: Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine, Vallodolid, Spain; and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Vallodolid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Yubero
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism*; D059305:Diet, High-Fat; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008055:Lipids
keywords: hypertension; insulin resistance; intermittent hypoxia; oxidative stress; sympathetic activity