Modulation of immunoreactive endothelin-1 (IR-ET-1) production by vasoactive substances was investigated in cultured endothelial cells (EC) derived from capillaries and microvessels of human brain. Peptides, catecholamines, thrombin, protein kinase C-activating phorbol ester, and calcium ionophore enhanced the secretion of IR-ET-1. The known vasoconstrictive peptides, angiotensin II and arginine-vasopressin dose-dependently stimulated the endothelial secretion of IR-ET-1. The angiotensin- and vasopressin-inducible production of IR-ET-1 was completely inhibited by their respective receptor antagonists [Sar(l), Ala(8))-angiotensin II and [1-6( beta -mercapto-beta,beta-cyclopentamethylene propionic acid), 2- O-methyltyrosine. The results indicate that the peptide-stimulated secretion of IR-ET-1 is receptor-mediated in EC which have specific angiotensin II and arginine-vasopressin receptors. These findings represent the first demonstration of IR-ET-1 production by capillary and microvascular endothelium of human brain.
