{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T14:11:45Z","timestamp":1758636705452},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,4,10]],"date-time":"2017-04-10T00:00:00Z","timestamp":1491782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009103","name":"Von-Behring-R\u00f6ntgen-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009103","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:label \/><jats:p>Nitric oxide (NO)\u2010deficiency as it occurs during endothelial dysfunction activates the endothelin\u20101 (ET\u20101) system and increases the expression of receptor activity modifying protein (RAMP)\u20101 that acts as a chaperon for calcium\u2010sensing receptors (CaR) that have recently been identified to improve cardiac function. Here, we hypothesized that ET\u20101 increases the cardiac expression of CaR and thereby induces an adaptive type of hypertrophy. Expressions of RAMP\u20101, endothelin receptors, and CaR were analyzed by RT\u2010PCR in left ventricular tissues of L\u2010NAME\u2010treated rats. Effects of ET\u20101 on CaR expression and cell function (load free cell shortening) were analyzed in adult rat ventricular cardiomyocytes. siRNA directed against CaR and RAMP\u20101 was used to investigate a causal relationship. PD142893 and BQ788 were used to dissect the contribution of ET<jats:sub>B1<\/jats:sub>, ET<jats:sub>B2<\/jats:sub>, and ET<jats:sub>A<\/jats:sub> receptors. Non\u2010specific NO synthase inhibition with L\u2010Nitro arginine methyl ester (L\u2010NAME) caused a cardiac upregulation of ET<jats:sub>B<\/jats:sub> receptors and CaR suggesting a paracrine effect of ET\u20101 on cardiomyocytes. Indeed, ET\u20101 induced the expression of CaR in cultured cardiomyocytes. Under these conditions, cardiomyocytes increased cell size (hypertrophy) but maintained normal function. Inhibition of ET<jats:sub>A<\/jats:sub> and ET<jats:sub>B1<\/jats:sub> receptors led to ET\u20101\u2010dependent reduction in cell shortening and attenuated up\u2010regulation of CaR. Down\u2010regulation of RAMP\u20101 reduced CaR responsiveness. In conclusion, ET\u20101 causes an adaptive type of hypertrophy by up\u2010regulation of CaR in cardiomyocytes via ET<jats:sub>A<\/jats:sub> and\/or ET<jats:sub>B1<\/jats:sub> receptors. J. Cell. Physiol. 232: 2508\u20132518, 2017. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25612","type":"journal-article","created":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T22:43:26Z","timestamp":1474670606000},"page":"2508-2518","source":"Crossref","is-referenced-by-count":3,"title":["The Role of Calcium\u2010Sensing Receptors in Endothelin\u20101\u2010Dependent Effects on Adult Rat Ventricular Cardiomyocytes: Possible Contribution to Adaptive Myocardial Hypertrophy"],"prefix":"10.1002","volume":"232","author":[{"given":"Elena","family":"Dyukova","sequence":"first","affiliation":[{"name":"Physiologisches Institut Justus\u2010Liebig\u2010Universit\u00e4t Gie\u00dfen Giessen Germany"},{"name":"Institute of Fundamental Medicine and Biology Kazan Federal University Kazan Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Schreckenberg","sequence":"additional","affiliation":[{"name":"Physiologisches Institut 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