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Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor

Abstract

Endothelium-derived vascular relaxing factor (EDRF)1 is a humoral agent that is released by vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine and bradykinin2. EDRF is very unstable, with a half-life of between 6 (refs 3, 4) and 50 (ref. 5) s, and is clearly distinguishable from prostacyclin6. The chemical structure of EDRF is unknown but it has been suggested that it is either a hydroperoxy- or free radical-derivative of arachidonic acid or an unstable aldehyde, ketone or lactone3. We have examined the role of superoxide anion (O2−) in the inactivation of EDRF released from vascular endothelial cells cultured on microcarrier beads and bioassayed using a cascade of superfused aortic smooth muscle strips7. With this system, we have now demonstrated that EDRF is protected from breakdown by superoxide dismutase (SOD) and Cu2+, but not by catalase, and is inactivated by Fe2+. These findings indicate that O2− contributes significantly to the instability of EDRF.

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Gryglewski, R., Palmer, R. & Moncada, S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320, 454–456 (1986). https://doi.org/10.1038/320454a0

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