Furchgott and nitric oxide in blood vessels

Acetylcholine widens blood vessels powerfully in the living body, yet in isolated helical strips of rabbit aorta the only response anyone had reported was contraction. Robert Furchgott, head of pharmacology at the State University of New York medical school in Brooklyn, had used rabbit aortic strips in his research for years.

In May 1978, in the first experiment of a new study of receptors in rabbit aorta, a technician's error gave a preparation in which acetylcholine and carbachol relaxed the muscle instead of contracting it. Furchgott and J. V. Zawadzki traced the difference. Rings of aorta relaxed; strips did not, because while being cut the inner surface of the strips had been rubbed against other surfaces. When rubbing was avoided, rings and strips of every shape relaxed. Rubbing, they suspected, stripped away the endothelium, the single layer of cells lining the vessel.

Their 1980 paper in Nature showed that acetylcholine relaxed rabbit aorta and other vessels only when endothelial cells were present. The drug acted on muscarinic receptors of those cells, which released something that relaxed the smooth muscle beneath. In a so-called sandwich experiment, a piece of aorta without endothelium, which contracted on stimulation, was laid against a piece with endothelium that could neither contract nor relax. Stimulated together, the bare piece relaxed. Furchgott called the unknown messenger endothelium-derived relaxing factor, or EDRF.

Ferid Murad had already shown in 1977 that nitroglycerin and related drugs release nitric oxide, which activates guanylyl cyclase, raises cyclic GMP and relaxes smooth muscle. In 1986 Louis Ignarro and Furchgott, working independently, concluded that EDRF was nitric oxide, and they presented the finding at a conference that July. Nitric oxide was the first gas found to act as a signaling molecule in the body. In atherosclerosis the endothelium makes less of it, and knowledge of its role in erection led to new drugs for impotence.

Furchgott, Ignarro and Murad shared the 1998 Nobel Prize in Physiology or Medicine. Furchgott died on 19 May 2009.