title: Neonatal intermittent hypoxia leads to long-lasting facilitation of acute hypoxia-evoked catecholamine secretion from rat chromaffin cells.
abstract: 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 ([Ca(2+)](i)) and these responses were attenuated, but not abolished, by treatments designed to eliminate Ca(2+) flux into cells (Ca(2+)-free medium or Cd(2+)), indicating that intracellular Ca(2+) 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 [Ca(2+)](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 [Ca(2+)](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 [Ca(2+)](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.
authors.affiliation: Department of Medicine, The Center for Systems Biology of O2Sensing, University of Chicago, MC 5068, Chicago, IL 60637, USA.
authors.forename: Dangjai
authors.initials: D
authors.lastname: Souvannakitti
authors.forename: Ganesh K
authors.initials: GK
authors.lastname: Kumar
authors.forename: Aaron
authors.initials: A
authors.lastname: Fox
authors.forename: Nanduri R
authors.initials: NR
authors.lastname: Prabhakar