EFFECT OF EXPOSURE TO HYPOXIA FROM BIRTH AN ALDOSTERONE IN RABBITS - ROLE OF UNESTERIFIED FATTY-ACIDS

Hypoxia and fluid and electrolyte disturbances are serious risks to no rmal postnatal development. Because a decrease in inspired O-2 (hypoxi c hypoxia) inhibits aldosterone synthesis in the adult and aldosterone controls water and electrolyte balance, we studied adrenocortical fun ction in rabbits exposed to normobaric normoxia or hypoxic hypoxia (fr action of inspired O-2 0.09) from birth. At 21 days of age, rabbits we re anesthetized, the adrenals were rapidly removed, and the adrenal ca psules 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% decr ease in adenosine 3',5'-cyclic monophosphate-stimulated aldosterone re lease in vitro. We hypothesized that increased unesterified fatty acid s could be partly responsible for inhibition of aldosterone synthesis. Total serum unesterified fatty acids in hypoxic kits were significant ly increased (298 +/- 14 mu mol/l) compared with 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 product ion was not affected by washing. Washing had no effect on aldosterone synthesis by cells from normoxic rats. Finally, exposing washed zona g lomerulosa cells to oleic acid (10-50 mu M) inhibited aldosteronogenes is. We conclude that exposure to hypoxia from birth attenuates aldoste rone production in part due to an increase in levels of unesterified f atty acid levels.