Coronary microvascular endothelial cells cosecrete angiotensin II and endothelin-1 via a regulated pathway

Although endothelial cells produce angiotensin II (ANG II) and endothelin-1 (ET-1), it is not clear whether a single cell produces both peptides, with cosecretion in response to stimulation, or whether different subpopulation s of endothelial cells secrete one or the other peptide, with secretion in response to different stimuli. Exposure of cultured coronary microvascular endothelial cells to cycloheximide for 60 min had no effect on ANG II or ET -1 secretion. This result suggested the existence of a preformed intracellu lar pool of ANG II and ET-1, which is a precondition for regulated secretio n. Exposure of endothelial cells to isoproterenol, high extracellular potas sium, or cadmium, all of which stimulate peptide secretion via different si gnaling pathways, significantly (P > 0.001) increased the secretion of both ANG II and ET-1 in a cell size-dependent manner. Sodium nitroprusside and S-nitroso-N-acetyl penicillamine significantly (P > 0.001) decreased ANG II and ET-1 secretion, whereas N-omega-nitro- L-arginine-methyl ester enhance d it. The similar regulation of ANG II and ET-1 secretion and the presence of both peptides around individual endothelial cells indicate that the auto crine/paracrine regulation of cardiovascular function by endothelial cells is accomplished via cosecretion of ANG II and ET-1.