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This Article Full Text Full Text (PDF) All Versions of this Article: 101/6/2837    most recent 00036.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Souvannakitti, D. Articles by Prabhakar, N. R. PubMed PubMed Citation Articles by Souvannakitti, D. Articles by Prabhakar, N. R.

Neonatal Intermittent Hypoxia Leads to Long-Lasting Facilitation of Acute Hypoxia-Evoked Catecholamine Secretion From Rat Chromaffin Cells

¹Department of Medicine and ²Department of Neurobiology, Pharmacology, and Physiology, The Center for Systems Biology of O₂Sensing, University of Chicago, Chicago, Illinois

Submitted 13 January 2009; accepted in final form 27 March 2009

The objective of the present study was to examine the effects of intermittent hypoxia (IH) and sustained hypoxia (SH) on hypoxia-evoked catecholamine (CA) secretion from chromaffin cells in neonatal rats and assess the underlying mechanism(s). Experiments were performed on rat pups exposed to either IH (15-s hypoxia/5-min normoxia; 8 h/day) or SH (hypobaric hypoxia, 0.4 atm) or normoxia (controls) from P0 to P5. IH treatment facilitated hypoxia-evoked CA secretion and elevations in the intracellular calcium ion concentration ([Ca²⁺]_i) and these responses were attenuated, but not abolished, by treatments designed to eliminate Ca²⁺ flux into cells (Ca²⁺-free medium or Cd²⁺), indicating that intracellular Ca²⁺ stores were augmented by IH. Norepinephrine (NE) and epinephrine (E) levels of adrenal medullae were elevated in IH-treated pups. IH treatment increased reactive oxygen species (ROS) production in adrenal medullae and antioxidant treatment prevented IH-induced facilitation of CA secretion, elevations in [Ca²⁺]_i by hypoxia, and the up-regulation of NE and E. The effects of neonatal IH treatment on hypoxia-induced CA secretion and elevation in [Ca²⁺]_i, CA, and ROS levels persisted in rats reared under normoxia for >30 days. In striking contrast, chromaffin cells from SH-treated animals exhibited attenuated hypoxia-evoked CA secretion. In SH-treated cells hypoxia-evoked elevations in [Ca²⁺]_i, NE and E contents, and ROS levels were comparable with controls. These observations demonstrate that: 1) neonatal IH and SH evoke opposite effects on hypoxia-evoked CA secretion from chromaffin cells, 2) ROS signaling mediates the faciltatory effects of IH, and 3) the effects of neonatal IH on chromaffin cells persist into adult life.