Differences in neuropeptide Y-induced secretion of endothelin-1 in left and right human endocardial endothelial cells

The aim of the study was to test the hypothesis that neuropeptide Y (NPY) may induce endothelin-1 (ET-1) secretion in left (hLEECs) and right (hREECs) human endocardial endothelial cells. Furthermore, the type of NPY receptor implicated could be different in NPY-induced secretion in hLEECs and hREECs. Using immunofluorescence coupled to real 3D confocal microscopy and ELISA, our results showed that stimulation of secretion by NPY induced the release of ET-1 from both right and left human ventricular endocardial endothelial cells (hEECs) in a time-dependent manner. Furthermore, the secretory capacity of hREECs was higher than that of hLEECs. In addition, our results showed that the effect of NPY on ET-1 secretion in hLEECs was only due to activation of Y5 receptors. However, the effect of NPY on ET-1 secretion in hREECs was due to mainly Y2 and partially Y5 receptors activation. In conclusion, our results suggest that differences in excitation-secretion coupling exist between hREECS and hLEECs which may contribute to the functional differences between right and left ventricular muscle. Furthermore, high NPY level contributes to ET-1 release by hEECs and Y2 and Y5 receptors antagonists may be used for regulation of ET-1 secretion in the heart.