Endothelium-Derived Relaxing Factor: Discovery, Early Studies, and Identifcation as Nitric Oxide (Nobel Lecture).

The presence of air bubbles, and thus the unintentional removal of endothelial cells, may have prevented the discovery of endothelium-dependent vasodilation at an earlier date. In investigations with perfused rabbit central ear artery the infusion of acetylcholine, a known potent prejunctional inhibitor of adrenergic neurotransmission, did not inhibit vasoconstriction produced by infused norepinephrine. It was later determined that air bubbles in the perfusion line had mechanically removed the endothelial cells, and as a result no release of endothelium-derived relaxing factor (EDRF) could take place.