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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.

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Related in: MedlinePlus

Effect of genotype and treatment on heart rate variability distinguished by gender.After 28 days with or without aldo/NaCl treatment animals were anaesthetized with isoflurane and electrocardiography recordings were obtained for at least ten minutes employing an Einthoven I limb lead recording, from these recordings heart rate variability was determined. SDNN (a, b), as standard deviation of RR interval of normal-to-normal intervals was analysed first. As no difference could be obtained in female animals, SD delta NN (standard deviation of averages of normal R-R intervals, c) and RMSSD (Square root of the mean of the sum of the squares of differences between adjacent NN intervals, d) was only analysed in male animals. Data are given as mean ± SEM, * p<0.05 compared to respective wildtype, # p<0.05 compared to respective control. N = 3–5 animals/group.
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f6: Effect of genotype and treatment on heart rate variability distinguished by gender.After 28 days with or without aldo/NaCl treatment animals were anaesthetized with isoflurane and electrocardiography recordings were obtained for at least ten minutes employing an Einthoven I limb lead recording, from these recordings heart rate variability was determined. SDNN (a, b), as standard deviation of RR interval of normal-to-normal intervals was analysed first. As no difference could be obtained in female animals, SD delta NN (standard deviation of averages of normal R-R intervals, c) and RMSSD (Square root of the mean of the sum of the squares of differences between adjacent NN intervals, d) was only analysed in male animals. Data are given as mean ± SEM, * p<0.05 compared to respective wildtype, # p<0.05 compared to respective control. N = 3–5 animals/group.

Mentions: The parameters for heart rate variability were not different in the female groups (Fig. 6B). In contrast, all three parameters were significantly enhanced by aldosterone/NaCl in male EGFR knockout animals (Fig. 6A, C and D), leading to an increased heart rate variability.


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)

Effect of genotype and treatment on heart rate variability distinguished by gender.After 28 days with or without aldo/NaCl treatment animals were anaesthetized with isoflurane and electrocardiography recordings were obtained for at least ten minutes employing an Einthoven I limb lead recording, from these recordings heart rate variability was determined. SDNN (a, b), as standard deviation of RR interval of normal-to-normal intervals was analysed first. As no difference could be obtained in female animals, SD delta NN (standard deviation of averages of normal R-R intervals, c) and RMSSD (Square root of the mean of the sum of the squares of differences between adjacent NN intervals, d) was only analysed in male animals. Data are given as mean ± SEM, * p<0.05 compared to respective wildtype, # p<0.05 compared to respective control. N = 3–5 animals/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Effect of genotype and treatment on heart rate variability distinguished by gender.After 28 days with or without aldo/NaCl treatment animals were anaesthetized with isoflurane and electrocardiography recordings were obtained for at least ten minutes employing an Einthoven I limb lead recording, from these recordings heart rate variability was determined. SDNN (a, b), as standard deviation of RR interval of normal-to-normal intervals was analysed first. As no difference could be obtained in female animals, SD delta NN (standard deviation of averages of normal R-R intervals, c) and RMSSD (Square root of the mean of the sum of the squares of differences between adjacent NN intervals, d) was only analysed in male animals. Data are given as mean ± SEM, * p<0.05 compared to respective wildtype, # p<0.05 compared to respective control. N = 3–5 animals/group.
Mentions: The parameters for heart rate variability were not different in the female groups (Fig. 6B). In contrast, all three parameters were significantly enhanced by aldosterone/NaCl in male EGFR knockout animals (Fig. 6A, C and D), leading to an increased heart rate variability.

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