Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 296, Issue 3, Pages R735-R742Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.90490.2008
Keywords
recurrent apneas; premature infants; chemoreflex; arterial chemoreceptors; chronic intermittent hypoxia
Categories
Funding
- National Heart, Lung, and Blood Institute [HL-076537, HL-086493, HL-090554]
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Pawar A, Nanduri J, Yuan G, Khan SA, Wang N, Kumar GK, Prabhakar NR. Reactive oxygen species-dependent endothelin signaling is required for augmented hypoxic sensory response of the neonatal carotid body by intermittent hypoxia. Am J Physiol Regul Integr Comp Physiol 296: R735-R742, 2009. First published December 24, 2008; doi:10.1152/ajpregu.90490.2008.-We previously reported that intermittent hypoxia (IH) augments hypoxic sensory response (HSR) and increases the number of glomus cells in neonatal carotid bodies. In the present study, we tested the hypothesis that recruitment of endothelin-1 (ET-1) signaling by reactive oxygen species (ROS) plays a critical role in IH-evoked changes in neonatal carotid bodies. Experiments were performed on neonatal rats exposed either to 10 days of IH (P0-P10; 8 h/day) or to normoxia. IH augmented HSR of the carotid bodies ex vivo and resulted in hyperplasia of glomus cells. The effects of IH were associated with enhanced basal release of ET-1 under normoxia, sensitization of carotid body response to exogenous ET-1, and upregulation of ETA but not an ETB receptor mRNA without altering the ET-1 content. An ETA but not ETB receptor antagonist prevented augmented HSR by IH. ROS levels were elevated in carotid bodies from IH-treated rat pups as evidenced by increased levels of malondialdehyde. Systemic administration of manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (MnTMPyP; 5 mg/kg ip), a scavenger of O-2(center dot-), prevented IH-induced elevation of ROS, basal release of ET-1, upregulation of ETA mRNA, and augmented HSR. In striking contrast, MnTMPyP treatment had no significant effect on IH-induced hyperplasia of glomus cells. These results demonstrate that IH-evoked increase in HSR involve a ROS-mediated increase in basal ET-1 release and upregulation of ETA receptor mRNA.
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