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The Role of Calcium‐Sensing Receptors in Endothelin‐1‐Dependent Effects on Adult Rat Ventricular Cardiomyocytes: Possible Contribution to Adaptive Myocardial Hypertrophy
Author(s) -
Dyukova Elena,
Schreckenberg Rolf,
Arens Christoph,
Sitdikova Guzel,
Schlüter KlausDieter
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25612
Subject(s) - receptor , medicine , endocrinology , endothelin receptor , downregulation and upregulation , endothelin 1 , muscle hypertrophy , paracrine signalling , ventricular hypertrophy , cell , chemistry , biology , microbiology and biotechnology , left ventricular hypertrophy , blood pressure , biochemistry , gene
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 ET B1 , ET B2 , and ET A receptors. Non‐specific NO synthase inhibition with L‐Nitro arginine methyl ester (L‐NAME) caused a cardiac upregulation of ET B 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 ET A and ET B1 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 ET A and/or ET B1 receptors. J. Cell. Physiol. 232: 2508–2518, 2017. © 2016 Wiley Periodicals, Inc.