Dr. Nicholas Penington Role of Nitric Oxide in the Vasculature:"Chance Favors the Prepared Mind"

Robert Furchgott's Discovery of the Role of Nitric Oxide in the Vasculature: "Chance favors the Prepared Mind" In May 1978, an accidental finding resulting from a technician's error (failing to remove the inner endothelial layer of a blood vessel) completely changed the course of research in Dr. Furchgott's laboratory. On a preparation of rabbit aorta, muscarinic agents such as acetylcholine induced relaxation rather than the expected contraction. This finding was perplexing, and Dr. Furchgott set out to determine why this happened. In 1981, Furchgott carried out the seminal "Sandwich Bioassay" - a novel experimental preparation that included both a section of intact vascular tissue, and a section of vascular tissue with the endothelial layer removed. In this experiment, Furchgott showed that, initially, the neurotransmitter acetylcholine did not cause relaxation in the vascular tissue without endothelium; however, when that tissue was sandwiched next to a section of intact vascular tissue, acetylcholine triggered the release of an "endothelial derived relaxing factor" from the intact preparation that transferred and caused relaxation in the neighboring preparation without its endothelium. Thus, from this pivotal experiment, Furchgott concluded that the ability of blood vessels to expand is dependent upon having an intact endothelium, and a substance that dilates blood vessels is formed in the endothelial layer of blood vessels when stimulated by acetylcholine. In 1982, Cherry and Furchgott coined the phrase EDRF and two years later Furchgott published the finding that hemoglobin inhibited the action of EDRF. In the spring of 1986, Dr. Furchgott suggested based on many experiments including those of Dr. Ferrid Murad that EDRF was Nitric Oxide. Dr. Louis Ignarro presented spectrographic evidence to confirm this conclusion. Since then, many new nitric oxide-based therapies have been developed, including medications used to treat cardiovascular and respiratory diseases and impotence.