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Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor

Why this mattered

Before Palmer, Ferrige, and Moncada’s 1987 Nature paper, endothelium-derived relaxing factor was chiefly an operational entity: a short-lived activity released by endothelial cells that relaxed vascular smooth muscle. The paper’s importance was to identify that activity with nitric oxide, showing that endothelial cells released NO in amounts sufficient to explain EDRF bioactivity, and that NO and EDRF shared the same instability and responses to hemoglobin and superoxide dismutase (paper record). This turned a mysterious vascular “factor” into a defined chemical messenger.

The paradigm shift was that a simple, diffusible gas could function as a physiological signal between cells. That made vascular tone, platelet inhibition, and endothelial function experimentally tractable in molecular terms: researchers could ask how NO was synthesized, how it activated soluble guanylate cyclase and cGMP signaling, and how loss of NO bioavailability contributed to hypertension, thrombosis, atherosclerosis, and other vascular diseases. Within a year, the same group showed endothelial NO synthesis from L-arginine, opening the way to nitric oxide synthase biology.

The paper also helped connect older pharmacology with modern signaling biology. Organic nitrates and nitrovasodilators could now be understood as acting through the same NO-cGMP pathway, while later work extended NO signaling into immunity and neuroscience. The broader discovery program was recognized by the 1998 Nobel Prize for nitric oxide as a cardiovascular signaling molecule, described by the Nobel committee as a new principle of biological signaling by a gas (Nobel Prize).

Abstract

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