Oxidative stress augments chemoreflex sensitivity in rats exposed to chronic intermittent hypoxia.
Chronic exposure to intermittent hypoxia (CIH) elicits plasticity of the carotid sinus and phrenic nerves via reactive oxygen species (ROS). To determine whether CIH-induced alterations in ventilation, metabolism, and heart rate are also dependent on ROS, we measured responses to acute hypoxia in conscious rats after 14 and 21 d of either CIH or normoxia (NORM), with or without concomitant administration of allopurinol (xanthine oxidase inhibitor), combined allopurinol plus losartan (angiotensin II type 1 receptor antagonist), or apocynin (NADPH oxidase inhibitor). Carotid body nitrotyrosine production was measured by immunohistochemistry. CIH produced an increase in the ventilatory response to acute hypoxia that was virtually eliminated by all three pharmacologic interventions. CIH caused a robust increase in carotid body nitrotyrosine production that was greatly attenuated by allopurinol plus losartan and by apocynin but unaffected by allopurinol. CIH caused a decrease in metabolic rate and a reduction in hypoxic bradycardia. Both of these effects were prevented by allopurinol, allopurinol plus losartan, and apocynin.
John Rankin Laboratory of Pulmonary Medicine, School of Medicine and Public Health: University of Wisconsin, Madison, WI 53706, USA; Department of Orthopedics and Rehabilitation, School of Medicine and Public Health; University of Wisconsin, Madison, WI 53706, USA. Electronic address: bjmorgan0107@gmail.com.
Barbara J
BJ
Morgan
Department of Health and Human Physiology, College of Liberal Arts and Sciences; University of Iowa, Iowa City, IA 52242, USA.
Melissa L
ML
Bates
Laboratory of Cardiorespiratory Control, Universidad Autónoma de Chile, Santiago, Chile.
Rodrigo Del
RD
Rio
Department of Surgical Sciences, School of Veterinary Medicine; University of Wisconsin, Madison, WI 53706, USA.
Zunyi
Z
Wang
Pharmacy Practice Division, School of Pharmacy; University of Wisconsin, Madison, WI 53705, USA.
John M
JM
Dopp
D000098:Acetophenones / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D002346:Carotid Sinus / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000473:pathology* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010991:Plethysmography; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012044:Regression Analysis; D012119:Respiration / Q000187:drug effects; D013990:Tidal Volume / Q000502:physiology; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000098:Acetophenones; D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D002395:Catecholamines; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D002245:Carbon Dioxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D000493:Allopurinol; C056165:acetovanillone; D019808:Losartan
Antioxidant; Chemoreceptor; Intermittent hypoxia; Reactive oxygen species