Biosynthesis and interaction of endothelium-derived vasoactive mediators.
The vascular endothelium, which envelopes the circulating blood in a continuous monolayer, is not only a physical barrier between blood and vessel wall, but a highly complex "organ" which is involved in the regulation of blood vessel tone and permeability, blood coagulation, angiogenesis, leukocyte and platelet reactivity, phagocytosis of bacteria and the metabolism of many vascular mediators. This article focuses on the biosynthesis, biological actions and interactions of endothelium-derived vasoactive mediators, namely, prostacyclin, endothelium-derived relaxing factor--now characterized as nitric oxide--and endothelin, in the regulation of blood vessel tone under physiological and pathophysiological conditions. The formation of these highly vasoactive substances in modulated by changes in intracellular messengers (cyclic adenosine monophosphate, cyclic guanosine monophosphate, calcium), by interactions of endothelium with blood-borne cells and plasma constituents and finally by the interaction of these mediators themselves. The current evidence supports the view that nitric oxide plays a pivotal role for the regulation of blood vessel tone under physiological conditions, while the generation of prostacyclin is primarily an important defense mechanism to maintain a sufficient blood vessel patency and tissue viability under conditions of a compromised blood supply. Although the physiological role of the endothelium-derived vasoconstrictor peptide endothelin-1 is less well defined, it is apparent that any potential harmful vasoconstrictor effects resulting from an enhanced formation of endothelin under pathophysiological conditions are modulated by the simultaneous generation of prostacyclin, nitric oxide and tissue-plasminogen activator, thus preventing excessive vasoconstriction and thrombotic occlusion of the vascular bed concerned.
Thiemermann
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William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
D000595:Amino Acid Sequence; D000818:Animals; D016232:Endothelins / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology
D016232:Endothelins; D009569:Nitric Oxide; D011464:Epoprostenol