title: Carotid body and cardiorespiratory alterations in intermittent hypoxia: the oxidative link.
abstract: Intermittent hypoxia, a feature of obstructive sleep apnoea, potentiates ventilatory hypoxic responses, alters heart rate variability and produces hypertension, partially owing to an enhanced carotid body responsiveness to hypoxia. Since oxidative stress is a potential mediator of both chemosensory and cardiorespiratory alterations, we hypothesised that an antioxidant treatment may prevent these alterations. Accordingly, we studied the effects of ascorbic acid (1.25 g.L(-1) drinking water) on plasma lipid peroxidation, nitrotyrosine and inducible nitric oxide synthase (iNOS) immunoreactivity in the carotid body, ventilatory and carotid chemosensory responses to acute hypoxia, heart rate variability and arterial blood pressure in male Sprague-Dawley rats exposed to 5% O(2); 12 episodes.h(-1); 8 h.day(-1) or sham condition for 21 days. Intermittent hypoxia increased plasma lipid peroxidation, nitrotyrosine and iNOS expression in the carotid body, enhanced carotid chemosensory and ventilatory hypoxic responses, modified heart rate variability and produced hypertension. Ascorbic acid prevented the increased plasma lipid peroxidation and nitrotyrosine formation within the carotid body, and the enhanced carotid chemosensory and ventilatory responses to hypoxia, as well as heart rate variability alterations and hypertension. The present results support an essential role for oxidative stress in the generation of carotid body chemosensory potentiation and systemic cardiorespiratory alterations induced by intermittent hypoxia.
authors.affiliation: Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla 114-D Santiago, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Del Rio
authors.forename: E A
authors.initials: EA
authors.lastname: Moya
authors.forename: R
authors.initials: R
authors.lastname: Iturriaga
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D002344:Carotid Body / Q000187:drug effects* / Q000503:physiopathology; D002628:Chemoreceptor Cells / Q000378:metabolism / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000209:etiology / Q000517:prevention & control*; D015227:Lipid Peroxidation; D008055:Lipids / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009602:Nitrosamines / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020181:Sleep Apnea, Obstructive / Q000150:complications*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D000975:Antioxidants; D008055:Lipids; D009602:Nitrosamines; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D001205:Ascorbic Acid