17β-Estradiol regulates the expression of endothelin receptor type B in the heart

摘要

class="enumerated" style="list-style-type:decimal">Little is known about the interaction of 17β-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 ETA-R and ETB-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 ETB-R mRNA (2.6±0.8-fold) in the left ventricular myocardium, which was not attendant with an alteration of ETA-R, ECE and ppET-1 mRNA expression.An upregulation of the relative expression level of ETB-R protein due to ovariectomy was also demonstrated by radioligand binding assay.Upregulation of both ETB-R mRNA and ETB-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 ETB-R mRNA in cardiomyocytes stimulated with E2. ETB-R downregulation was not attendant with the alteration of ETA-R, ECE and ppET-1 mRNA expression.Taken together, these data demonstrate that estrogen regulates the expression of ETB-R in rat ventricular myocardium in vivo and in vitro. These observations may help to understand gender-based differences found in cardiovascular disease.