Paradoxical conservation of cardiac and renal arachidonate content in essential fatty acid deficiency.

The effects of essential fatty acid (EFA) deprivation on the arachidonate content and phospholipid composition of different tissues are quite diverse. When C57B1 mice were placed on a fat-free diet, hepatic liquids were readily depleted of arachidonate. In contrast, the renal cortex tenaciously retained arachidonate, whereas surprisingly the heart showed a doubling of its content of arachidonate. This increase in cardiac arachidonate was due to a four-fold increase in arachidonylphosphatidylethanolamine (PE). The renal cortex showed preservation of its arachidonate content in PE, phosphatidylserine, and phosphatidylcholine. Only phosphatidylinositol was depleted of arachidonate in heart or renal cortex. Using an in vivo labeling technique, it was shown that the liver incorporated most of the [1-14C]arachidonate initially following intraperitoneal injection. Over 11 days, as levels of labeled arachidonate fell in liver, the EFA-deficient heart accumulated arachidonate selectively in PE (8-fold greater than control), and the EFA-deficient renal cortex accumulated arachidonate in PE, phosphatidylserine, and phosphatidylcholine (2-3-fold greater than control). This uptake was shown to be specific for arachidonate over 20:3(n-9). Despite the conservation of cardiac and renal arachidonate seen with EFA deficiency, prostaglandin production by the isolated perfused EFA-deficient heart and kidney was markedly decreased relative to control in response to specific agonist stimulation with angiotensin II, although it was equivalent to control in response to nonspecific stimulation by ischemia. These data suggest that the liver serves to supply other tissues with arachidonate in EFA deficiency, and that the heart and renal cortex both contain mechanisms to accumulate arachidonate selectively in certain phospholipids. However, phosphatidylinositol, which is uniquely depleted of arachidonate in heart and renal cortex with EFA deficiency, appears to be the principal source of arachidonate in response to receptor-mediated agonists.