ABSTRACT

Although the existence of the molecule nitric oxide (NO) – a single nitrogen molecule bound to a single oxygen molecule, which together forms a free radical gas – has been known for years, it was only with the publication of a series of papers in the 1980s that the biological importance of this mediator was appreciated. In 1980, Furchgott1 showed that blood vessel endothelium actively released a factor which maintained vessels in a moderately dilated state. This factor was highly unstable, and its chemical properties were initially undefined. In view of its biological properties it was named endothelium-derived relaxing factor (EDRF). In the few years following, both Furchgott2 and Ignarro3 independently showed that EDRF was similar in its properties to NO. Thereafter, in 1987, Palmer et al4

showed that EDRF released from endothelial cells by stimulation with bradykinin was found to have identical effects to NO on contraction of rat aorta that had been denuded of endothelium. Furthermore, the sensitivity of rat aorta to EDRF and to NO declined at similar rates, the half-life of both agents was identical, both were inhibited in a similar manner and amount by hemoglobin, and the activity of both was prolonged by superoxide dismutase. Lastly, L-arginine was the precursor to both NO and EDRF production. Thus, EDRF and NO are biologically and chemically identical. Ignarro et al5 published similar results that same year, and Ignarro ultimately received the Nobel prize for medicine for his work on NO together with Furchgott and Murad.