Respiratory plasticity after perinatal hyperoxia is not prevented by antioxidant supplementation.

Abstract

Perinatal hyperoxia attenuates the hypoxic ventilatory response in rats by altering development of the carotid body and its chemoafferent neurons. In this study, we tested the hypothesis that hyperoxia elicits this plasticity through the increased production of reactive oxygen species (ROS). Rats were born and raised in 60% O(2) for the first two postnatal weeks while treated with one of two antioxidants: vitamin E (via milk from mothers whose diet was enriched with 1000 IU vitamin E kg(-1)) or a superoxide dismutase mimetic, manganese(III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP; via daily intraperitoneal injection of 5-10 mg kg(-1)); rats were subsequently raised in room air until studied as adults. Peripheral chemoreflexes, assessed by carotid sinus nerve responses to cyanide, asphyxia, anoxia and isocapnic hypoxia (vitamin E experiments) or by hypoxic ventilatory responses (MnTMPyP experiments), were reduced after perinatal hyperoxia compared to those of normoxia-reared controls (all P<0.01); antioxidant treatment had no effect on these responses. Similarly, the carotid bodies of hyperoxia-reared rats were only one-third the volume of carotid bodies from normoxia-reared controls (P <0.001), regardless of antioxidant treatment. Protein carbonyl concentrations in the blood plasma, measured as an indicator of oxidative stress, were not increased in neonatal rats (2 and 8 days of age) exposed to 60% O(2) from birth. Collectively, these data do not support the hypothesis that perinatal hyperoxia impairs peripheral chemoreceptor development through ROS-mediated oxygen toxicity.

• Authors: Ryan W Bavis, Julie M Wenninger, Brooke M Miller, Elizabeth F Dmitrieff, E Burt Olson Jr, Gordon S Mitchell, Gerald E Bisgard
• Journal: Respiratory physiology & neurobiology (Respir Physiol Neurobiol) Vol. 160 Issue 3 Pg. 301-12 (Feb 29 2008) ISSN: 1569-9048 [Print] Netherlands
• PMID: 18069076 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antioxidants
• Metalloporphyrins
• Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin
• Vitamin E
• Sodium Cyanide

Topics

• Analysis of Variance
• Animals
• Animals, Newborn
• Anorexia (physiopathology, prevention & control)
• Antioxidants (administration & dosage)
• Asphyxia (physiopathology, prevention & control)
• Carotid Sinus (drug effects)
• Dose-Response Relationship, Drug
• Drug Interactions
• Hyperoxia (pathology, prevention & control)
• Metalloporphyrins (administration & dosage)
• Phrenic Nerve (drug effects, physiopathology)
• Protein Carbonylation (drug effects)
• Rats
• Rats, Sprague-Dawley
• Sodium Cyanide (pharmacology)
• Vitamin E (administration & dosage)