Ferid Murad, MD, PhD at 80: A Legacy of Science, Medicine, and Mentorship for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system

It is hard to believe that it is has been nearly twenty years since the Nobel Prize was awarded for the discovery of nitric oxide to Robert Furchgott, Louis Ignarro, and Ferid Murad. This, and the many other awards that these investigators received over the years, recognized the paradigm-changing importance of their discovery that a gas like nitric oxide could function as a hormone and mediate signaling that was essential to the physiology and pathophysiology in the cardiovascular, and virtually all other biological, systems. Individually, they contributed pieces to the puzzle that ultimately brought these novel molecular insights into specific relief. Dr. Furchgott was the first to recognize the generation by the endothelium of a signaling molecule that relaxed vascular smooth muscle, termed endothelium-derived relaxing factor. Dr. Ignarro’s work, in parallel with Dr. Furchgott, revealed that EDRF was actually nitric oxide, the active agent which produced smooth muscle relaxation. In a separate series of studies, Dr. Murad revealed that nitrovasodilators exerted their predominant pharmacologic effect on blood vessel relaxation because they served as a source for nitric oxide generation. Moreover, he demonstrated that the primary biological receptor for nitric oxide was cytosolic, or soluble, guanylate cyclase which regulated vascular smooth muscle contractility through the enzymatic conversion of GTP to the second messenger cyclic GMP.