Wei Lun Visiting Professorial Lecture: Nitric oxide in the regulation of vascular function: an historical overview.

The field of nitric oxide (NO) research has developed in explosive proportions since the discovery of endogenous NO in 1986. The biological importance of NO was first shown by the findings that nitroglycerin causes vasodilation by liberating NO in the smooth muscle, and activating guanylate cyclase to raise smooth muscle levels of cyclic GMP. NO also inhibits platelet aggregation by cyclic GMP mechanisms. NO activates guanylate cyclase by heme dependent mechanisms involving the formation of a nitrosyl-heme complex. The high pharmacological potency of NO was finally understood when NO was shown to be formed endogenously, and to be the same as EDRF. Based on these properties of NO, new drugs can be developed as vasodilators and antiplatelet agents for the treatment of a variety of vascular disorders including impotency. NO elicits many other actions in mammalian systems including inhibition of cell proliferation, airway bronchodilation, antimicrobial effects, other host defense effects, and also modulates learning and memory as well as other central functions. This allows for an extensive opportunity to develop novel drugs for the diagnosis, prevention, and treatment of a number of different diseases, many of which are vascular in origin.