The Discovery of Nitric Oxide as the Endogenous Nitrovasodilator

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1988-10, Vol.12 (4), p.365-372
• Main Authors: MONCADA, SALVADOR, PALMER, RICHARD M. J, HIGGS, E ANNIE
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biological Factors - pharmacology; Blood vessels and receptors; Epoprostenol - physiology; Fundamental and applied biological sciences. Psychology; Humans; Nitric Oxide - metabolism; Nitric Oxide - pharmacology; Vasodilator Agents - pharmacology; Vertebrates: cardiovascular system
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.12.4.365

Endothelium-derived relaxing factor (EDRF) is a labile humoral agent released by vascular endotheHum that mediates the relaxation induced by some vasodilators, including acetylchollne and bradykinin. EDRF also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to vascular endotbetium. These actions of EDRF are mediated through stimulation of the soluble guanylate cydase and the consequent elevation of cyclic guanosine 3ʼ,5ʼ-monophosphate. EDRF has been identified as nitric oxide (NO). The pharmacology of NO and EDRF is indistinguishable; furthermore, sufficient NO is released from endothellal cells to account for the biological activities of EDRF. Organic nitrates exert then- vasodilator activity following conversion to NO in vascular smooth musde cells. Thus, NO may be considered the endogenous nitrovasodilator. NO is synthesized by vascular endotheUum from the terminal guanido nitrogen atom(s) of the amino add L-arginine. This indicates the existence of an enzymic pathway in which L-arginine is the endogenous precursor for the synthesis of NO. The discovery of the release of NO by vascular endotheiial cells, the blosynthetk pathway leading to its generation, and its interaction with other vasoactive substances opens up new avenues for research into the physiology and pathophysioiogy of the vessd wall.