Cultured Astrocytes Release a Factor that Decreases Endothelin‐1 Secretion by Brain Microvessel Endothelial Cells

Abstract: Endothelin‐1 (ET‐1), originally characterized as a potent vasoconstrictor peptide secreted by vascular endothelial cells, has now been described to possess a wide range of biological activities within the cardiovascular system and in other organs. Brain microvessel endothelial cells, which, together with perivascular astrocytes, constitute the blood‐brain barrier, have been shown to secrete ET‐1, whereas specific ET‐1 receptors are expressed on astrocytes. It is reported here that conditioned medium from primary cultures of mouse embryo astrocytes could significantly, and reversibly, attenuate the accumulation of both ET‐1 and its precursor big ET‐1 in the supernatant of rat brain microvessel endothelial cells by up to 59 and 76%, respectively, as assessed by immunometric assay. This inhibitor of ET‐1 production was purified by gel‐exclusion and ion‐exchange chromatography as a 280‐Da iron‐containing molecule, able to release nitrites upon degradation. These results suggest that astrocytes, via release of an iron‐nitrogen oxide complex, may be involved in a regulatory loop of ET‐1 production at the level of the blood‐brain barrier.