Isoforms of nitric oxide synthase: functions in the cardiovascular system.
Various cell types, including endothelial cells, can synthesize nitric oxide (NO). Three different isoforms of NO synthase have been characterized, purified and cloned. Isozyme I is present in neuronal cells of the brain (where NO may mediate synaptic plasticity), in peripheral non-adrenergic non-cholinergic (NANC) neurons (where NO acts as an atypical neurotransmitter relaxing vascular and non-vascular smooth muscle), and in various specialized epithelial cells. Macrophages can be induced with bacterial endotoxin and/or cytokines to express isozyme II. The high concentrations of NO produced by this isoform have cytostatic effects on parasitic microorganisms and tumour cells. A similar isozyme can be induced in the vascular wall (presumably in smooth muscle cells) in sepsis and during cytokine therapy. The large amounts of NO produced by this enzyme contribute to the symptoms of septic shock, such as vasodilatation and microvascular endothelial damage. Endothelial cells contain isoform III of NO synthase which seems to be unique for this cell type. Endothelium-derived NO is a physiologically significant vasodilator and inhibitor of platelet aggregation and adhesion. In addition, vascular NO can prevent leukocyte adhesion to the endothelium by interfering with the adhesion molecule CD11/CD18, and NO has also been shown to inhibit the proliferation of vascular smooth muscle cells. Hence, NO represents a protective factor against vascular damage and probably atherogenesis.
Förstermann
U
U
Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany.
Nakane
M
M
Tracey
W R
WR
Pollock
J S
JS
D000594:Amino Acid Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism*; D008322:Mammals; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D009420:Nervous System / Q000201:enzymology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase; D012772:Shock, Septic / Q000201:enzymology
D007527:Isoenzymes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases