AJP - Heart and Circulatory Physiology, Vol 249, Issue 6 1188-H1194, Copyright © 1985 by American Physiological Society
Mechanisms of accumulation of arachidonic acid in cultured myocardial cells during ATP depletion
M. D. Gunn, A. Sen, A. Chang, J. T. Willerson, L. M. Buja and K. R. Chien
Previous studies have suggested that the accumulation of free arachidonic
acid may be of major importance in the pathophysiology of myocardial
ischemia. The purpose of the present study was to determine if the release
of arachidonic acid from myocardial cells was more dependent on the extent
of ATP depletion than on the inhibition of fatty acid oxidation. In
addition, these studies were designed to determine if arachidonic acid
release only occurred when ATP was depleted beyond a critical threshold
level. To examine the relationship between arachidonic acid release and ATP
depletion, cultured myocardial cells from neonatal rat hearts were labeled
with [3H]arachidonate and [14C]palmitate. In response to ATP depletion with
various metabolic inhibitors, [3H]arachidonic acid and [14C]palmitic acid
were released from phospholipids. Phosphatidylcholine,
phosphatidylethanolamine, and phosphatidic acid were the major esterified
sources of the arachidonate. The release of both fatty acids was related to
the extent of ATP depletion and not whether a glycolytic or respiratory
inhibitor was utilized. Various combinations and doses of metabolic
inhibitors were used, and experimental conditions that produced a greater
than 75% decrease in ATP content were associated with the accumulation of
arachidonic acid. These results suggest that an ATP-dependent step may be
linked to the accumulation of arachidonic acid during myocardial ATP
depletion. It is suggested that myocardial cells may release arachidonic
acid directly in response to ATP depletion.
