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17 β ‐Estradiol regulates the expression of endothelin receptor type B in the heart
Author(s) -
Nuedling Simone,
Eickels Martin van,
Alléra Axel,
Doevendans Pieter,
Meyer Rainer,
Vetter Hans,
Grohé Christian
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705409
Subject(s) - downregulation and upregulation , endothelin 1 , ovariectomized rat , endocrinology , messenger rna , medicine , endothelin receptor , receptor , biology , estrogen , chemistry , gene , biochemistry
Little is known about the interaction of 17 β ‐estradiol (E2) and the vasoactive endothelin system in the heart. Endothelin signaling is activated in a failing heart and may contribute to myocardial dysfunction and remodeling. Therefore, we investigated the regulation of proteins of the endothelin system (ppET‐1, ECE and ET A ‐R and ET B ‐R) in the hearts of female spontaneously hypertensive rats (SHR) with respect to E2. Relative expression levels of the respective cardiac mRNA obtained from sham‐operated, ovariectomized and ovariectomized E2‐substituted SHR were quantified by real‐time PCR. Ovariectomy led to a significant upregulation of the ET B ‐R mRNA (2.6±0.8‐fold) in the left ventricular myocardium, which was not attendant with an alteration of ET A ‐R, ECE and ppET‐1 mRNA expression. An upregulation of the relative expression level of ET B ‐R protein due to ovariectomy was also demonstrated by radioligand binding assay. Upregulation of both ET B ‐R mRNA and ET B ‐R protein expression was completely inhibited by E2 replacement. To confirm these results in in vitro experiments, we quantified the mRNA of ET‐R subtypes from isolated cardiomyocytes in the presence and absence of E2 (10 −8 M , 24 h). Our data showed a markedly downregulated level of ET B ‐R mRNA in cardiomyocytes stimulated with E2. ET B ‐R downregulation was not attendant with the alteration of ET A ‐R, ECE and ppET‐1 mRNA expression. Taken together, these data demonstrate that estrogen regulates the expression of ET B ‐R in rat ventricular myocardium in vivo and in vitro . These observations may help to understand gender‐based differences found in cardiovascular disease.British Journal of Pharmacology (2003) 140 , 195–201. doi: 10.1038/sj.bjp.0705409