The discovery that the paramagnetic, free radical gas nitric oxide (NO) is the chemical species responsible for endothelium-dependent relaxation of large blood vessels, neurotransmission in the central and peripheral nervous systems, and activated macrophage function of the innate immune system has forged the convergence of several disciplines to study the mechanisms of NO biosynthesis in mammals and lower organisms. The global importance of NO as a highly regulated, second-messenger gas throughout the body culminated in the focused efforts of many laboratories worldwide to understand its synthesis, spectrum of activities, and metabolism. Based on the accolades ascribed to the field of NO biology, which led to a Nobel Prize in Medicine and Physiology awarded to Ignarro, Murad, and Furchgott in 1998, it could be argued that the discovery of the NO signaling pathway was a major paradigm shift in our understanding of endothelial and blood vessel function, an attribute shared by few other discoveries in vascular biology.

HISTORICAL PERSPECTIVES

The role of NO gas in the biological sciences has a long history, including its function as an environmental pollutant, as an active ingredient of gunpowder, and as the therapeutic antianginal nitroglycerin. In keeping with the focus of this volume, our historical perspective is considered from the vascular point of view.

Although the convergence of many disparate lines of scientific enquiry was responsible for the ground-swell of work in the field of NO biology, the defining moment for NO biology in the cardiovascular system and its vasoregulatory role of the endothelium in general hinged on the pioneering work of Robert Furchgott (1).