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Research Article Free access | 10.1172/JCI113522

Endothelium-dependent relaxation is independent of arachidonic acid release.

P G Milner, N J Izzo Jr, J Saye, A L Loeb, R A Johns, and M J Peach

Department of Medicine, University of Virginia School of Medicine, Charlottesville 22908.

Find articles by Milner, P. in: PubMed | Google Scholar

Department of Medicine, University of Virginia School of Medicine, Charlottesville 22908.

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Department of Medicine, University of Virginia School of Medicine, Charlottesville 22908.

Find articles by Saye, J. in: PubMed | Google Scholar

Department of Medicine, University of Virginia School of Medicine, Charlottesville 22908.

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Department of Medicine, University of Virginia School of Medicine, Charlottesville 22908.

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Department of Medicine, University of Virginia School of Medicine, Charlottesville 22908.

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Published June 1, 1988 - More info

Published in Volume 81, Issue 6 on June 1, 1988
J Clin Invest. 1988;81(6):1795–1803. https://doi.org/10.1172/JCI113522.
© 1988 The American Society for Clinical Investigation
Published June 1, 1988 - Version history
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Abstract

Endothelium-dependent relaxation is mediated by the release from vascular endothelium of an endothelium-derived relaxing factor (EDRF). It is not clear what role arachidonic acid has in this process. Inhibition of phospholipase A2, and diacylglycerol lipase in cultured bovine aortic endothelial cells caused a marked reduction in agonist-induced arachidonic acid release from membrane phospholipid pools, and complete inhibition of prostacyclin production. EDRF release, assayed by measuring endothelium-dependent cGMP changes in mixed endothelial-smooth muscle cell cultures, was not inhibited under these conditions. In fact, EDRF release in response to two agonists, melittin and ATP, was actually increased in cells treated with phospholipase A2 inhibitors. In addition, pretreatment of rats with high-dose dexamethasone, an inhibitor of PLA2, did not attenuate endothelium-dependent relaxation in intact aortic rings removed from the animals, or depressor responses in anesthetized animals induced by endothelium-dependent vasodilators. In summary, inhibition of arachidonic acid release from membrane phospholipid pools does not attenuate endothelium-dependent relaxation in rats, or the release and/or response to EDRF in cultured cells.

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