title: Moderate inappropriately high aldosterone/NaCl constellation in mice: cardiovascular effects and the role of cardiovascular epidermal growth factor receptor.
abstract: Non-physiological activation of the mineralocorticoid receptor (MR), e.g. by aldosterone under conditions of high salt intake, contributes to the pathogenesis of cardiovascular diseases, although beneficial effects of aldosterone also have been described. The epidermal growth factor receptor (EGFR) contributes to cardiovascular alterations and mediates part of the MR effects. Recently, we showed that EGFR is required for physiological homeostasis and function of heart and arteries in adult animals. We hypothesize that moderate high aldosterone/NaCl, at normal blood pressure, affects the cardiovascular system depending on cardiovascular EGFR. Therefore we performed an experimental series in male and female animals each, using a recently established mouse model with EGFR knockout in vascular smooth muscle cells and cardiomyocytes and determined the effects of a mild-high aldosterone-to-NaCl constellation on a.o. marker gene expression, heart size, systolic blood pressure, impulse conduction and heart rate. Our data show that (i) cardiac tissue of male but not of female mice is sensitive to mild aldosterone/NaCl treatment, (ii) EGFR knockout induces stronger cardiac disturbances in male as compared to female animals and (iii) mild aldosterone/NaCl treatment requires the EGFR in order to disturb cardiac tissue homeostasis whereas beneficial effects of aldosterone seem to be independent of EGFR.
authors.affiliation: Julius-Bernstein-Institute of Physiology, Medical Faculty, University of Halle-Wittenberg, Halle, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Schreier
authors.affiliation: Julius-Bernstein-Institute of Physiology, Medical Faculty, University of Halle-Wittenberg, Halle, Germany.
authors.forename: Sindy
authors.initials: S
authors.lastname: Rabe
authors.affiliation: Julius-Bernstein-Institute of Physiology, Medical Faculty, University of Halle-Wittenberg, Halle, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Winter
authors.affiliation: Julius-Bernstein-Institute of Physiology, Medical Faculty, University of Halle-Wittenberg, Halle, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ruhs
authors.affiliation: Julius-Bernstein-Institute of Physiology, Medical Faculty, University of Halle-Wittenberg, Halle, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Mildenberger
authors.affiliation: Julius-Bernstein-Institute of Physiology, Medical Faculty, University of Halle-Wittenberg, Halle, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Schneider
authors.affiliation: Institute of Cancer Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
authors.affiliation: Max-Delbrück-Center for Molecular Medicine (MDC), Berlin-Buch, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gotthardt
authors.affiliation: Institute of Pharmacy, Faculty of Natural Sciences 1, University of Halle-Wittenberg, Halle, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kempe
authors.affiliation: Institute of Pharmacy, Faculty of Natural Sciences 1, University of Halle-Wittenberg, Halle, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
authors.affiliation: Julius-Bernstein-Institute of Physiology, Medical Faculty, University of Halle-Wittenberg, Halle, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Grossmann
authors.affiliation: Julius-Bernstein-Institute of Physiology, Medical Faculty, University of Halle-Wittenberg, Halle, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gekle
mesh_terms: D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D066246:ErbB Receptors / Q000502:physiology*; D005260:Female; D006706:Homeostasis; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D012965:Sodium Chloride / Q000378:metabolism* / Q000494:pharmacology; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D012965:Sodium Chloride; D000450:Aldosterone; C541485:EGFR protein, mouse; D066246:ErbB Receptors