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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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Effect of genotype and treatment on electrocardiography parameters distinguished by gender.After 28days 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. PR interval (a, e) was measured from the beginning of the P wave to the start of the chamber complex, P duration (b, f) was defined as the time from start to end of the P wave, QRS interval (c, g) was measured from start to end of the chamber excitation and the QTc interval (d,h; time from start of the chamber excitation to the end of the chamber repolarization, heartrate corrected according to Bazette). 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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f5: Effect of genotype and treatment on electrocardiography parameters distinguished by gender.After 28days 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. PR interval (a, e) was measured from the beginning of the P wave to the start of the chamber complex, P duration (b, f) was defined as the time from start to end of the P wave, QRS interval (c, g) was measured from start to end of the chamber excitation and the QTc interval (d,h; time from start of the chamber excitation to the end of the chamber repolarization, heartrate corrected according to Bazette). 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: Electrocardiography was performed to analyze the electrical conduction in the heart. Electrical conduction (P-duration, PR-, QRS and QTc-interval) did not differ between the female groups (Fig. 5E–H), by contrast to the male groups (Fig. 5A–D), where EGFR-KO caused prolonged P-duration and QRS- as well as QTc-intervals (and a PR-prolongation in tendency) that were reversed by aldosterone/NaCl-treatment. The observed prolongation mirrors at least in part the cardiac hypertrophy.


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 electrocardiography parameters distinguished by gender.After 28days 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. PR interval (a, e) was measured from the beginning of the P wave to the start of the chamber complex, P duration (b, f) was defined as the time from start to end of the P wave, QRS interval (c, g) was measured from start to end of the chamber excitation and the QTc interval (d,h; time from start of the chamber excitation to the end of the chamber repolarization, heartrate corrected according to Bazette). 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

f5: Effect of genotype and treatment on electrocardiography parameters distinguished by gender.After 28days 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. PR interval (a, e) was measured from the beginning of the P wave to the start of the chamber complex, P duration (b, f) was defined as the time from start to end of the P wave, QRS interval (c, g) was measured from start to end of the chamber excitation and the QTc interval (d,h; time from start of the chamber excitation to the end of the chamber repolarization, heartrate corrected according to Bazette). 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: Electrocardiography was performed to analyze the electrical conduction in the heart. Electrical conduction (P-duration, PR-, QRS and QTc-interval) did not differ between the female groups (Fig. 5E–H), by contrast to the male groups (Fig. 5A–D), where EGFR-KO caused prolonged P-duration and QRS- as well as QTc-intervals (and a PR-prolongation in tendency) that were reversed by aldosterone/NaCl-treatment. The observed prolongation mirrors at least in part the cardiac hypertrophy.

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