Carotid body inflammation and cardiorespiratory alterations in intermittent hypoxia

• Published in: The European respiratory journal Vol. 39; no. 6; pp. 1492 - 1500
• Main Authors: DEL RIO, Rodrigo, MOYA, Esteban A, PARGA, María J, MADRID, Carlos, ITURRIAGA, Rodrigo
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.06.2012
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiology. Vascular system; Cardiovascular System - drug effects; Cardiovascular System - physiopathology; Carotid Body - drug effects; Carotid Body - physiopathology; Chronic Disease; Disease Models, Animal; Hypertension - drug therapy; Hypertension - physiopathology; Hypoxia - drug therapy; Hypoxia - physiopathology; Ibuprofen - therapeutic use; Inflammation - drug therapy; Inflammation - physiopathology; Interleukin-1beta - analysis; Male; Medical sciences; Pneumology; Proto-Oncogene Proteins c-fos - analysis; Rats; Rats, Sprague-Dawley; Respiration - drug effects; Respiratory system : syndromes and miscellaneous diseases; Sleep Apnea, Obstructive - drug therapy; Sleep Apnea, Obstructive - physiopathology; Solitary Nucleus - chemistry; Tumor Necrosis Factor-alpha - analysis; Hypertension; Nervous system diseases; Oxygen; Sleep apnea syndrome; Respiratory disease; Alteration; Cardiovascular disease; Inflammation; obstructive sleep apnoea; Intermittent; Carotid; Hypoxia; Body; Pneumology
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00141511

Chronic intermittent hypoxia (CIH), a main feature of obstructive sleep apnoea (OSA), increases hypoxic ventilatory responses and elicits hypertension, partially attributed to an enhance carotid body (CB) responsiveness to hypoxia. As inflammation has been involved in CIH-induced hypertension and chemosensory potentiation, we tested whether ibuprofen may block CB chemosensory and cardiorespiratory alterations induced by CIH in a rat model of OSA. We studied the effects of ibuprofen (40 mg · kg(-1) · day(-1)) on immunohistochemical interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels in the CB, the number of c-fos-positive neurons in the nucleus tractus solitarii (NTS), CB chemosensory and ventilatory responses to hypoxia, and arterial blood pressure in male rats either exposed for 21 days to 5% O(2) (12 episodes · h(-1), 8 h · day(-1)) or kept under sham condition. CIH increased CB TNF-α and IL-1β and c-fos-positive neurons in the NTS, enhanced carotid chemosensory and ventilatory hypoxic responses, and produced hypertension. Ibuprofen prevented CB cytokine overexpression and CIH-induced increases in c-fos-positive neurons in the NTS, the enhanced hypoxic ventilatory responses and hypertension, but failed to impede the CB chemosensory potentiation. Results suggest that pro-inflammatory cytokines may contribute to the CIH-induced cardiorespiratory alterations, acting at several levels of the hypoxic chemoreflex and cardiovascular control pathways.