Effect of intracellular Ca2+ concentration on endothelin‐1 secretion

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Abstract
The role of intracellular free Ca2+ concentration ([Ca2+]i in cellular regulation of endothelin‐(ET‐1) secretion was investigated in cultured porcine aortic endothelial cells of first passage. Intracellular Ca2+ concentration were adjusted between 50 nM and 1 μM using EGTA and thapsigargin, respectively. ET‐1 secretion was maximal at [Ca2+]i of 190–470 nM, and reduced at low (50 and 110 nM) and high (470 nM) [Ca2+]i. The Ca2+ ionophores A23187 and ionomycin (each 1 μM), both of which raise [Ca2+]i above 1 μM, also potently inhibited ET‐1 secretion under basal and stimulated conditions. The A23187‐induced reduction in ET‐1 secretion was not affected by N G‐nitro‐l‐arginine (0.1 mM). Our results provide evidence that basal ET‐1 secretion is regulated by Ca2+ and that Ca2+ ionophores reduce ET‐1 secretion due to the inhibitory effect of high [Ca2+]i.