The effect of exposure to hypoxia from birth on aldosterone in
rabbits: role of unesterified fatty acids.
Raff, Hershel, Barbara M. Jankowski, Theodore L. Goodfriend, John E.
Baker, Paula E. Papanek.
Endocrine Research Laboratory (HR, BMJ, PEP), St. Luke's Medical
Center, Milwaukee, WI 53215, Departments of Medicine (HR) and
Cardiothoracic Surgery (JEB), Medical College of Wisconsin,
Milwaukee, WI 53226, Program in Physical Therapy (PEP), Marquette
University, Milwaukee, WI 53201, Middleton Memorial Veterans Hospital
and the Departments of Medicine and Pharmacology, University of
Wisconsin School of Medicine (TLG), Madison, WI 53705
APStracts 3:0399R, 1996.
Hypoxia and fluid and electrolyte disturbances are serious risks to
normal post-natal development. Since a decrease in inspired O2
(hypoxic hypoxia) inhibits aldosterone synthesis in the adult and
aldosterone controls water and electrolyte balance, we
studieddrenocortical function in rabbits exposed to normobaric
normoxia or hypoxic hypoxia (FIO2 0.09) from birth. At 21 days of
age, rabbits were anesthetized, the adrenals were rapidly removed,
and the adrenal capsules containing mostly zona glomerulosa cells
were separated. Cells were dispersed with collagenase and studied in
vitro. Hypoxia in vivo resulted in a 73% decrease in basal
aldosterone release and a 86% decrease in cAMP-stimulated aldosterone
release in vitro. We hypothesized that increased unesterified fatty
acids could be partly responsible for inhibition of aldosterone
synthesis. Total serum unesterified fatty acids in hypoxic kits were
significantly increased (298+/-14 [mu]mol/L) compared to normoxic
kits (184+/-31 [mu]mol/L). When cells from hypoxic rabbits were
washed with fatty acid-free albumin and studied under conditions
devoid of fatty acids, aldosterone production was partially restored.
Corticosterone production was not affected by washing. Washing had no
effect on aldosterone synthesis by cells from normoxic rats. Finally,
exposing washed zona glomerulosa cells to oleic acid (10-50 [mu]M)
inhibited aldosteronogenesis. We conclude that exposure to hypoxia
from birth attenuates aldosterone production in part due to an
increase in levels of unesterified fatty acid levels.
Received 9 May 1996; accepted in final form 30 October 1996.
APS Manuscript Number R262-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996