title: [Nitric oxide: the endogenous nitrate in the cardiovascular system].
abstract: The endothelium takes part in the regulation of vascular tone through the production of endothelium-derived relaxing and contracting factors. The L-arginine pathway within endothelial cells in the blood vessel wall is the source of production of the endogenous nitrovasodilator, nitric oxide (NO). The NO molecule has one unpaired electron and readily reacts with oxygen, superoxide radicals, or transition metals. Therefore the measurement of the concentration of NO in biological systems is a challenging analytical problem. NO is formed from L-arginine via constitutive NO synthase. It is released under basal conditions and in response to mechanical stimuli such as shear stress and in response to receptor-operated agonists such as bradykinin, serotonin, ADP/ATP, thrombin, histamine and substance P. NO is the mediator of endothelium-dependent relaxation in the circulation and exerts its effects by activating soluble guanylyl cyclase in vascular smooth muscle, which in turn leads to the formation of cyclic guanosine monophosphate (cyclic GMP) and to relaxation. In addition to its effect on vascular smooth muscle, NO is also released albuminally to interact with circulating platelets. Increases in cyclic GMP in platelets are associated with a decreased adhesion and aggregation. In endothelial cells, NO inhibits its own production as well as that of the vasoconstrictor peptide endothelin-1. Thus, endothelium-derived NO, through its vasodilator and anti-aggregatory properties, prevents vasospasm and thrombus formation in the circulation and thereby helps to maintain blood flow to vital organs such as the heart. Under certain conditions such as inflammation, NO may also be formed via inducible nitric oxide synthase by smooth muscle cells, endothelium and monocytes. Therapeutic nitrates also exert their effects by releasing NO from their molecules and activating soluble guanylyl cyclase. Their effects are particularly pronounced in arteries in which the release of NO is inhibited or impaired or in the absence of the endothelium. Thus, the endothelial L-arginine pathway plays an important protective role in the local regulation of blood flow and through its vasodilator and antiplatelet properties. Nitrates can at least in part substitute the endogenous nitrovasodilator in disease states with impaired formation of NO.
authors.affiliation: Department Medizin, Inselspital Bern/Schweiz.
authors.forename: M R
authors.initials: MR
authors.lastname: Tschudi
authors.forename: T F
authors.initials: TF
authors.lastname: Lüscher
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D010973:Platelet Adhesiveness / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D009569:Nitric Oxide
vernacular_title: Stickstoffmonoxid: Das endogene Nitrat im Kreislauf.