Nitric oxide and the vascular endothelium.
The vascular endothelium synthesises the vasodilator and anti-aggregatory mediator nitric oxide (NO) from L-arginine. This action is catalysed by the action of NO synthases, of which two forms are present in the endothelium. Endothelial (e)NOS is highly regulated, constitutively active and generates NO in response to shear stress and other physiological stimuli. Inducible (i)NOS is expressed in response to immunological stimuli, is transcriptionally regulated and, once activated, generates large amounts of NO that contribute to pathological conditions. The physiological actions of NO include the regulation of vascular tone and blood pressure, prevention of platelet aggregation and inhibition of vascular smooth muscle proliferation. Many of these actions are a result of the activation by NO of the soluble guanylate cyclase and consequent generation of cyclic guanosine monophosphate (cGMP). An additional target of NO is the cytochrome c oxidase, the terminal enzyme in the electron transport chain, which is inhibited by NO in a manner that is reversible and competitive with oxygen. The consequent reduction of cytochrome c oxidase leads to the release of superoxide anion. This may be an NO-regulated cell signalling system which, under certain circumstances, may lead to the formation of the powerful oxidant species, peroxynitrite, that is associated with a variety of vascular diseases.
Moncada
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The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK. s.moncada@ucl.ac.uk
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D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism; D002448:Cell Adhesion; D049109:Cell Proliferation; D003576:Electron Transport Complex IV / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase
D004791:Enzyme Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D003576:Electron Transport Complex IV; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase