Limits...
Moderate inappropriately high aldosterone/NaCl constellation in mice: cardiovascular effects and the role of cardiovascular epidermal growth factor receptor.

Schreier B, Rabe S, Winter S, Ruhs S, Mildenberger S, Schneider B, Sibilia M, Gotthardt M, Kempe S, Mäder K, Grossmann C, Gekle M - Sci Rep (2014)

Bottom Line: Recently, we showed that EGFR is required for physiological homeostasis and function of heart and arteries in adult animals.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.

View Article: PubMed Central - PubMed

Affiliation: Julius-Bernstein-Institute of Physiology, Medical Faculty, University of Halle-Wittenberg, Halle, Germany.

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.

Show MeSH

Related in: MedlinePlus

Alteration of marker gene expression in hearts of female animals regarding genotype and treatment.After 28 days with or without aldo/NaCl treatment animals were sacrificed, the hearts dissected and snap frozen in liquid nitrogen. Gene expression was analysed according to the -Δ/Δct- method normalizing the individual mRNA amount to 18S and the mean mRNA amount in the untreated wildtype. In each graph the Δ/Δct amount is given on the left y-axis while the corresponding fold change in expression is given on the right y-axis. Data are given as mean ± SEM, * p<0.05 compared to respective wildtype, # p<0.05 compared to respective control. N = 6–12 animals/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4262830&req=5

f8: Alteration of marker gene expression in hearts of female animals regarding genotype and treatment.After 28 days with or without aldo/NaCl treatment animals were sacrificed, the hearts dissected and snap frozen in liquid nitrogen. Gene expression was analysed according to the -Δ/Δct- method normalizing the individual mRNA amount to 18S and the mean mRNA amount in the untreated wildtype. In each graph the Δ/Δct amount is given on the left y-axis while the corresponding fold change in expression is given on the right y-axis. Data are given as mean ± SEM, * p<0.05 compared to respective wildtype, # p<0.05 compared to respective control. N = 6–12 animals/group.

Mentions: In the hearts (Fig. 8) of female knockout animals the expression of Nppa, Nppb and Nos1 was enhanced compared to wildtype females. The expression of all other mRNAs investigated was not altered.


Moderate inappropriately high aldosterone/NaCl constellation in mice: cardiovascular effects and the role of cardiovascular epidermal growth factor receptor.

Schreier B, Rabe S, Winter S, Ruhs S, Mildenberger S, Schneider B, Sibilia M, Gotthardt M, Kempe S, Mäder K, Grossmann C, Gekle M - Sci Rep (2014)

Alteration of marker gene expression in hearts of female animals regarding genotype and treatment.After 28 days with or without aldo/NaCl treatment animals were sacrificed, the hearts dissected and snap frozen in liquid nitrogen. Gene expression was analysed according to the -Δ/Δct- method normalizing the individual mRNA amount to 18S and the mean mRNA amount in the untreated wildtype. In each graph the Δ/Δct amount is given on the left y-axis while the corresponding fold change in expression is given on the right y-axis. Data are given as mean ± SEM, * p<0.05 compared to respective wildtype, # p<0.05 compared to respective control. N = 6–12 animals/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262830&req=5

f8: Alteration of marker gene expression in hearts of female animals regarding genotype and treatment.After 28 days with or without aldo/NaCl treatment animals were sacrificed, the hearts dissected and snap frozen in liquid nitrogen. Gene expression was analysed according to the -Δ/Δct- method normalizing the individual mRNA amount to 18S and the mean mRNA amount in the untreated wildtype. In each graph the Δ/Δct amount is given on the left y-axis while the corresponding fold change in expression is given on the right y-axis. Data are given as mean ± SEM, * p<0.05 compared to respective wildtype, # p<0.05 compared to respective control. N = 6–12 animals/group.
Mentions: In the hearts (Fig. 8) of female knockout animals the expression of Nppa, Nppb and Nos1 was enhanced compared to wildtype females. The expression of all other mRNAs investigated was not altered.

Bottom Line: Recently, we showed that EGFR is required for physiological homeostasis and function of heart and arteries in adult animals.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.

View Article: PubMed Central - PubMed

Affiliation: Julius-Bernstein-Institute of Physiology, Medical Faculty, University of Halle-Wittenberg, Halle, Germany.

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.

Show MeSH
Related in: MedlinePlus