The role of chemical mediators released by the endothelium in the control of the cardiovascular system.

The vascular endothelium is much more than just a lining for blood vessels. It inactivates many mediators and produces a host of active substances. The production of these substances is modulated by interactions between the endothelial cells and white blood cells, platelets or constituents of plasma. The endothelial cells can be activated by amines, peptides, proteins, nucleotides, arachidonic acid and its metabolites, as well as by physical changes such as pulse pressure. This activation of endothelial cells is often mediated by specific receptors which respond in a variety of ways including the generation of prostacyclin and endothelium-derived relaxing factor (EDRF). Both of these mediators inhibit platelet aggregation and cause vascular dilatation, prostacyclin through increasing cyclic AMP, and EDRF through increasing cyclic GMP. EDRF has been identified as nitric oxide (NO) derived from the guanidino group of L-arginine. Inhibitors of NO formation cause a strong increase in blood pressure, showing that under normal conditions there is a constant formation of NO to dilate the vasculature. Endothelin is another agent made by endothelial cells; characterized and synthesized in 1988, it is the most potent vasoconstrictor so far discovered. Three endothelin isomers have been identified; paradoxically, ET-1 strongly releases both prostacyclin and NO, thus modulating its own vasoconstrictor activities.