The discovery that the biological actions of endothelium-derived relaxing factor (Furchgott and Zawadzki, 1980) are due to the endogenous release of nitric oxide (NO) c (Palmer et al., 1987; Ignarro et al., 1987; Khan and Furchgott, 1987) revealed the existence of a ubiquitous biochemical pathway (Moncada et al., 1989). NO is formed from the amino acid L-arginine by a family of enzymes, the NO synthases (NOSs), and plays a role in many physiological functions. Its formation in vascular endothelial cells, in response to chemical stimuli and to physical stimuli such as shear stress, maintains a vasodilator tone that is essential for the regulation of blood flow and pressure (Moncada et al., 1989; Vanhoutte, 1989; Furchgott, 1990; Ignarro, 1990; Vane et al., 1990; Luscher, 1991). NO produced by the endothelium and/or platelets also inhibits platelet aggregation and adhesion, inhibits leukocyte adhesion and modulates smooth muscle cell proliferation (Moncada and Higgs, 1993). NO is synthesized in neurons of the central nervous system, where it acts as a neuromediator with many physiological functions, including the formation of memory, coordination between neuronal activity and blood flow, and modulation of pain (Garthwaite, 1991; Snyder and Bredt, 1992). In the peripheral nervous system, NO is now known to be the mediator released by a widespread network of nerves, previously recognized as nonadrenergic and noncholinergic. These nerves mediate some forms of neurogenic vasodilation and regulate certain gastrointestinal, respiratory and genitourinary functions (Gillespie et al., 1990; Rand, 1992; Toda, 1995). These physiological actions of NO are mediated by activation of the soluble guanylate cyclase and consequent a Composition of the nitric oxide research subcommittee of the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification: M. Feelisch, Department of Nitric Oxide Research, Schwarz Pharma AG, Monheim, Germany; R. Furchgott, State University of New York Health Science Center at Brooklyn, Department of Pharmacology, Brooklyn, New York; J. Garthwaite, The Cruciform Project, University College London, London, United Kingdom; JB Hibbs, Jr., Veterans Affairs Medical Center and Department of Medicine, Division of Infectious Diseases, University of Utah Medical Center, Salt Lake City, Utah; A. Higgs, The Cruciform Project, University College London, London, United Kingdom; L. Ignarro, University of California, Los Angeles School of Medicine, Department of Molecular Biology, Los Angeles, California; T. Luscher, Division of Cardiology, University Hospital Bern, Bern, Switzerland; MA Marletta, College of Pharmacy, School of Medicine, University of Michigan, Ann Arbor, Michigan; W. Martin, University of Glasgow, Clinical Research Initiative, Glasgow, Scotland; S. Moncada, The Cruciform Project, University College London, London, United Kingdom; M. Rand, Royal Melbourne Institute of Technology, Department of Medical Laboratory Science, Melbourne, Australia; M. Spedding, Institut de Recherches Servier, Centre de Recherches de Croissy, Croissy sur Seine, France; S. Snyder, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland; N. Toda, Department of Pharmacology, Shiga University of Medical Sciences, Seta, Japan; JR Vane, The William Harvey Research Institute, St. Bartholomew’s Hospital Medical College, London, United Kingdom; P. Vanhoutte, Institut de Recherches International Servier, Courbevoie, France. b Address correspondence to: Salvador Moncada, The Cruciform Project, University College London, 140 Tottenham …