Endothelium-derived vasoactive agents, AT1 receptors and inflammation.
Angiotensin II, through activation of the angiotensin II-type 1 receptor, induces generation of inflammatory mediators in the blood vessel wall and as such plays an active role in the inflammation process. Direct stimulation of reactive oxygen species and nuclear factors seem to be key mechanisms through which this receptor induces inflammation. Inflammatory molecules are also known to modify endothelial cell function, especially endothelium-derived vasoactive agents, and inflammation is increasingly recognized as primary cause of major vascular disorders. There is accumulating evidence that stimulation of the type 1 angiotensin II receptor participates in vascular dysfunction by reducing activity of the endothelium-derived relaxants nitric oxide and hyperpolarizing factors. Furthermore activation of this angiotensin II receptor also enhances generation of endothelium-derived constricting factors, such as endothelin-1. This change in endothelial cell output not only impairs blood vessel relaxation but leads to pro-inflammatory and pro-coagulation conditions that are associated with disease initiation and progression. Pharmacological inhibitors of the angiotensin II pathway and the type 1 receptor subtype are in current clinical use for the treatment of hypertension. However evidence supports that these agents have a positive therapeutic benefit in other vascular pathologies with recognized inflammatory etiology, such as atherosclerosis.
University of the West of Scotland, School of Science, Paisley, PA1 2BE, Scotland, UK. andrew.mackenzie@uws.ac.uk
Andrew
A
MacKenzie
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology; D014652:Vascular Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D016207:Cytokines; D019332:Endothelin-1; D045462:Endothelium-Dependent Relaxing Factors; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1