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How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains.

Combe R, Mudgett J, El Fertak L, Champy MF, Ayme-Dietrich E, Petit-Demoulière B, Sorg T, Herault Y, Madwed JB, Monassier L - PLoS ONE (2016)

Bottom Line: High-salt/normal potassium vs.High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry).Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges.

View Article: PubMed Central - PubMed

Affiliation: Institut Clinique de la Souris, Institut de Génétique et de Biologie Moléculaire, Université de Strasbourg, Illkirch, France.

ABSTRACT

Background: Mouse transgenesis has provided the unique opportunity to investigate mechanisms underlying sodium kidney reabsorption as well as end organ damage. However, understanding mouse background and the experimental conditions effects on phenotypic readouts of engineered mouse lines such as blood pressure presents a challenge. Despite the ability to generate high sodium and chloride plasma levels during high-salt diet, observed changes in blood pressure are not consistent between wild-type background strains and studies.

Methods: The present work was designed in an attempt to determine guidelines in the field of salt-induced hypertension by recording continuously blood pressure by telemetry in mice submitted to different sodium and potassium loaded diets and changing experimental conditions in both C57BL/6N and C57BL/6J mice strain (Normal salt vs. Low salt vs. High-salt/normal potassium vs. High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry).

Results: In this study, we have shown that, despite a strong blood pressure (BP) basal difference between C57BL/6N and C57BL/6J mice, High salt/normal potassium diet increases BP and heart rate during the active phase only (dark period) in the same extent in both strains. On the other hand, while potassium level has no effect on salt-induced hypertension in C57BL/6N mice, high-salt/low potassium diet amplifies the effect of the high-salt challenge only in C57BL/6J mice. Indeed, in this condition, salt-induced hypertension can also be detected during light period even though this BP increase is lower compared to the one occurring during the dark period. Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges.

Conclusions: Therefore, to carry investigations on salt-induced hypertension in mice, chronic telemetry and studies in the active phase are essential prerequisites.

No MeSH data available.


Related in: MedlinePlus

Comparison between C57BL/6N and C57BL/6J for their mean blood pressure and heart rate responses to various salt challenges.Mice were monitored with telemetry during the dark (A, B) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17 and n = 17, for C57BL/6N and C57BL/6J respectively), LS = low salt diet (n = 15 and n = 17, for C57BL/6N and C57BL/6J respectively), HS = high Na+/normal K+ diet (n = 8 and n = 8, for C57BL/6N and C57BL/6J respectively) and HS/LK = high Na+/low K+ diet (n = 6 and n = 9, for C57BL/6N and C57BL/6J respectively). One-way ANOVA per light phase followed by Tukey’s post-hoc test; *: p<0.05 compared to NS diet; #: p<0.05 HS/LK compared to HS.
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pone.0153472.g002: Comparison between C57BL/6N and C57BL/6J for their mean blood pressure and heart rate responses to various salt challenges.Mice were monitored with telemetry during the dark (A, B) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17 and n = 17, for C57BL/6N and C57BL/6J respectively), LS = low salt diet (n = 15 and n = 17, for C57BL/6N and C57BL/6J respectively), HS = high Na+/normal K+ diet (n = 8 and n = 8, for C57BL/6N and C57BL/6J respectively) and HS/LK = high Na+/low K+ diet (n = 6 and n = 9, for C57BL/6N and C57BL/6J respectively). One-way ANOVA per light phase followed by Tukey’s post-hoc test; *: p<0.05 compared to NS diet; #: p<0.05 HS/LK compared to HS.

Mentions: Whatever the applied salt regimen, C57BL/6J mice had a higher BP than C57BL/6N animals (+10±1mmHg; Fig 2A). In a modified light/dark cycle, LS diet modified neither the BP nor the HR in both substrains (Fig 2A and 2B). Similar to C57BL/6N, when fed a HS diet, C57BL/6J mice showed an increase in BP and HR in the dark period (+12mmHg in C57BL/6N and +10mmHg in C57BL/6J; Fig 2A) whereas BP was comparable between NS and HS fed mice during the light period (Fig 2C). In addition, a similar HR increase was also observed in the two substrains during the dark period (575±14bpm vs. 629±8bpm in C57BL/6N and 582±14mmHg vs. 615±8bpm in C57BL/6J; NS vs. HS; Fig 2B).


How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains.

Combe R, Mudgett J, El Fertak L, Champy MF, Ayme-Dietrich E, Petit-Demoulière B, Sorg T, Herault Y, Madwed JB, Monassier L - PLoS ONE (2016)

Comparison between C57BL/6N and C57BL/6J for their mean blood pressure and heart rate responses to various salt challenges.Mice were monitored with telemetry during the dark (A, B) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17 and n = 17, for C57BL/6N and C57BL/6J respectively), LS = low salt diet (n = 15 and n = 17, for C57BL/6N and C57BL/6J respectively), HS = high Na+/normal K+ diet (n = 8 and n = 8, for C57BL/6N and C57BL/6J respectively) and HS/LK = high Na+/low K+ diet (n = 6 and n = 9, for C57BL/6N and C57BL/6J respectively). One-way ANOVA per light phase followed by Tukey’s post-hoc test; *: p<0.05 compared to NS diet; #: p<0.05 HS/LK compared to HS.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4835052&req=5

pone.0153472.g002: Comparison between C57BL/6N and C57BL/6J for their mean blood pressure and heart rate responses to various salt challenges.Mice were monitored with telemetry during the dark (A, B) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17 and n = 17, for C57BL/6N and C57BL/6J respectively), LS = low salt diet (n = 15 and n = 17, for C57BL/6N and C57BL/6J respectively), HS = high Na+/normal K+ diet (n = 8 and n = 8, for C57BL/6N and C57BL/6J respectively) and HS/LK = high Na+/low K+ diet (n = 6 and n = 9, for C57BL/6N and C57BL/6J respectively). One-way ANOVA per light phase followed by Tukey’s post-hoc test; *: p<0.05 compared to NS diet; #: p<0.05 HS/LK compared to HS.
Mentions: Whatever the applied salt regimen, C57BL/6J mice had a higher BP than C57BL/6N animals (+10±1mmHg; Fig 2A). In a modified light/dark cycle, LS diet modified neither the BP nor the HR in both substrains (Fig 2A and 2B). Similar to C57BL/6N, when fed a HS diet, C57BL/6J mice showed an increase in BP and HR in the dark period (+12mmHg in C57BL/6N and +10mmHg in C57BL/6J; Fig 2A) whereas BP was comparable between NS and HS fed mice during the light period (Fig 2C). In addition, a similar HR increase was also observed in the two substrains during the dark period (575±14bpm vs. 629±8bpm in C57BL/6N and 582±14mmHg vs. 615±8bpm in C57BL/6J; NS vs. HS; Fig 2B).

Bottom Line: High-salt/normal potassium vs.High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry).Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges.

View Article: PubMed Central - PubMed

Affiliation: Institut Clinique de la Souris, Institut de Génétique et de Biologie Moléculaire, Université de Strasbourg, Illkirch, France.

ABSTRACT

Background: Mouse transgenesis has provided the unique opportunity to investigate mechanisms underlying sodium kidney reabsorption as well as end organ damage. However, understanding mouse background and the experimental conditions effects on phenotypic readouts of engineered mouse lines such as blood pressure presents a challenge. Despite the ability to generate high sodium and chloride plasma levels during high-salt diet, observed changes in blood pressure are not consistent between wild-type background strains and studies.

Methods: The present work was designed in an attempt to determine guidelines in the field of salt-induced hypertension by recording continuously blood pressure by telemetry in mice submitted to different sodium and potassium loaded diets and changing experimental conditions in both C57BL/6N and C57BL/6J mice strain (Normal salt vs. Low salt vs. High-salt/normal potassium vs. High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry).

Results: In this study, we have shown that, despite a strong blood pressure (BP) basal difference between C57BL/6N and C57BL/6J mice, High salt/normal potassium diet increases BP and heart rate during the active phase only (dark period) in the same extent in both strains. On the other hand, while potassium level has no effect on salt-induced hypertension in C57BL/6N mice, high-salt/low potassium diet amplifies the effect of the high-salt challenge only in C57BL/6J mice. Indeed, in this condition, salt-induced hypertension can also be detected during light period even though this BP increase is lower compared to the one occurring during the dark period. Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges.

Conclusions: Therefore, to carry investigations on salt-induced hypertension in mice, chronic telemetry and studies in the active phase are essential prerequisites.

No MeSH data available.


Related in: MedlinePlus