Submitted on January 13, 2009
Revised on March 27, 2009
Accepted on March 27, 2009
Neonatal Intermittent Hypoxia Leads to Long-Lasting Facilitation of Acute Hypoxia-evoked Catecholamine Secretion from Rat Chromaffin Cells
Dangjai Souvannakitti1, Ganesh K. Kumar1, Aaron Fox2, and Nanduri R. Prabhakar1*
1 University of Chicago
2 The University of Chicago
* To whom correspondence should be addressed. E-mail: nanduri{at}uchicago.edu.
The objective of the present study was to examine the effects of intermittent (IH) and sustained hypoxia (SH) on hypoxia-evoked CA secretion from chromaffin cells in neonatal rats and assess the underlying mechanism(s). Experiments were performed on rat pups exposed to either IH (15s hypoxia-5min normoxia; 8h/day) or SH (hypobaric hypoxia; 0.4ATM) or normoxia (controls) from P0-P5. IH treatment facilitated hypoxia- evoked CA secretion and elevations in [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 anti-oxidant treatment prevented IH-induced facilitation of CA secretion, elevations in [Ca2+]i by hypoxia as well as the up-regulation of NE and E. The effects of neonatal IH treatment on hypoxia-induced CA secretion, elevation in [Ca2+]i, CA and ROS levels persisted in rats reared under normoxia for more than 30days. 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: a) neonatal IH and SH evoke opposite effects on hypoxia-evoked CA secretion from chromaffin cells, b) ROS signaling mediates the faciltatory effects of IH and c) the effects of neonatal IH on chromaffin cells persist into adult life.
