Neonatal intermittent hypoxia leads to long-lasting facilitation of acute hypoxia-evoked catecholamine secretion from rat chromaffin cells.
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.
Souvannakitti
Dangjai
D
Department of Medicine, The Center for Systems Biology of O2Sensing, University of Chicago, MC 5068, Chicago, IL 60637, USA.
Kumar
Ganesh K
GK
Fox
Aaron
A
Prabhakar
Nanduri R
NR