Abstract
More than a decade ago, the existence of an extremely labile and potent endogenous vasodilator synthesized by the endothelium, termed endothelium-derived relaxing factor (EDRF), was established by Furchgott and Zawadzki [1]. The nature of EDRF since remained elusive until experimental results from several laboratories identified it as the free radical nitric oxide (NO) [2,3]. Because it has a single unpaired electron, NO is also considered to be a free radical [4]. Molecular targets of NO are diverse, including heme proteins, non-heme iron-sulfur enzymes, DNA, and reactive oxygen species such as superoxide anion [5, 6]. Depending on its nature, the target molecule can either be activated (e.g. the heme-protein soluble guanylate cyclase) or inhibited (e.g. the non-heme iron protein ferritin) as a result of reacting with NO. In vascular smooth muscle, the molecular target of NO is the soluble enzyme guanylate cyclase [7]. Stimulation of the latter by NO increases the level of the second messenger cyclic guanosine monophosphate (cGMP) within vascular smooth muscle, thereby causing vasorelaxation [8]. The biochemistry of NO synthesis is remarquably simple, as to the nature of its precursors. The nitrogen atom of NO is derived from the N-guanidino terminal of the amino acid, L-arginine, whereas the oxygen atom is provided by molecular oxygen [7]. NO is synthesized from these two precursors by a newly discovered family of enzymes, the NO synthases (NOS).The complementary DNA for various isoforms of the NOS family have been recently cloned, and their amino acid primary structure sequenced [9]. There are two major subgroups of NOS isoforms, the constitutive and the inducible one. Endothelial NOS are predominantly constitutive, and most certainly play a key role in the modulation of systemic [10] and pulmonary [11] vascular tone.
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Dinh-Xuan, A.T., Brunet, F., Dhainaut, J.F. (1995). Inhaled Nitric Oxide: The Light and Shadow of a Therapeutic Breakthrough. In: Fink, M.P., Payen, D. (eds) Role of Nitric Oxide in Sepsis and ADRS. Update in Intensive Care and Emergency Medicine, vol 24. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79920-4_26
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DOI: https://doi.org/10.1007/978-3-642-79920-4_26
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