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Am J Physiol Heart Circ Physiol 279: H1087-H1096, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 3, H1087-H1096, September 2000

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

Yasuko Kusaka2, Ralph A. Kelly2, Gordon H. Williams1, and Imre Kifor1

1 Division of Endocrinology-Hypertension and 2 Division of Cardiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachuesetts 02115

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 subpopulations 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 intracellular pool of ANG II and ET-1, which is a precondition for regulated secretion. Exposure of endothelial cells to isoproterenol, high extracellular potassium, or cadmium, all of which stimulate peptide secretion via different signaling 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 Nomega -nitro-L-arginine-methyl ester enhanced it. The similar regulation of ANG II and ET-1 secretion and the presence of both peptides around individual endothelial cells indicate that the autocrine/paracrine regulation of cardiovascular function by endothelial cells is accomplished via cosecretion of ANG II and ET-1.

autocrine/paracrine regulation; parallel-acting messengers; intercellular communication via multiple messengers


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