Journalartikel

Jahr der Veröffentlichung: 2017

Seiten: 2508-2518

Zeitschrift: Journal of Cellular Physiology

Bandnummer: 232

Heftnummer: 9

ISSN: 0021-9541

eISSN: 1097-4652

DOI Link: https://doi.org/10.1002/jcp.25612

Verlag: Wiley

Abstract: 
Nitric oxide (NO)-deficiency as it occurs during endothelial dysfunction activates the endothelin-1 (ET-1) system and increases the expression of receptor activity modifying protein (RAMP)-1 that acts as a chaperon for calcium-sensing receptors (CaR) that have recently been identified to improve cardiac function. Here, we hypothesized that ET-1 increases the cardiac expression of CaR and thereby induces an adaptive type of hypertrophy. Expressions of RAMP-1, endothelin receptors, and CaR were analyzed by RT-PCR in left ventricular tissues of L-NAME-treated rats. Effects of ET-1 on CaR expression and cell function (load free cell shortening) were analyzed in adult rat ventricular cardiomyocytes. siRNA directed against CaR and RAMP-1 was used to investigate a causal relationship. PD142893 and BQ788 were used to dissect the contribution of ETB1, ETB2, and ETA receptors. Non-specific NO synthase inhibition with L-Nitro arginine methyl ester (L-NAME) caused a cardiac upregulation of ETB receptors and CaR suggesting a paracrine effect of ET-1 on cardiomyocytes. Indeed, ET-1 induced the expression of CaR in cultured cardiomyocytes. Under these conditions, cardiomyocytes increased cell size (hypertrophy) but maintained normal function. Inhibition of ETA and ETB1 receptors led to ET-1-dependent reduction in cell shortening and attenuated up-regulation of CaR. Down-regulation of RAMP-1 reduced CaR responsiveness. In conclusion, ET-1 causes an adaptive type of hypertrophy by up-regulation of CaR in cardiomyocytes via ETA and/or ETB1 receptors. (C) 2016 Wiley Periodicals, Inc.

Harvard-Zitierstil: Dyukova, E., Schreckenberg, R., Arens, C., Sitdikova, G. and Schlueter, K. (2017) The Role of Calcium-Sensing Receptors in Endothelin-1-Dependent Effects on Adult Rat Ventricular Cardiomyocytes: Possible Contribution to Adaptive Myocardial Hypertrophy, Journal of Cellular Physiology, 232(9), pp. 2508-2518. https://doi.org/10.1002/jcp.25612

APA-Zitierstil: Dyukova, E., Schreckenberg, R., Arens, C., Sitdikova, G., & Schlueter, K. (2017). The Role of Calcium-Sensing Receptors in Endothelin-1-Dependent Effects on Adult Rat Ventricular Cardiomyocytes: Possible Contribution to Adaptive Myocardial Hypertrophy. Journal of Cellular Physiology. 232(9), 2508-2518. https://doi.org/10.1002/jcp.25612