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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

Effects of high-salt/normal potassium and high-salt/low potassium on mean blood pressure and heart rate in C57BL/6N mice.Mice were monitored with telemetry in the dark (A, B, C) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17), LS = low salt diet (n = 15), HS = high Na+/normal K+ diet (n = 8) and HS/LK = high Na+/low K+ diet (n = 6). 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.g003: Effects of high-salt/normal potassium and high-salt/low potassium on mean blood pressure and heart rate in C57BL/6N mice.Mice were monitored with telemetry in the dark (A, B, C) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17), LS = low salt diet (n = 15), HS = high Na+/normal K+ diet (n = 8) and HS/LK = high Na+/low K+ diet (n = 6). 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: In C57BL/6N mice, when compared to normal potassium, the HS low potassium (HS/LK) intake did not affect the dark period BP increase that was superimposable in both groups (Fig 3A). Noteworthy, no statistically significant change in BP was observed during both HS/LK and HS diets during the light period (Fig 2C). Interestingly, HS/LK challenge prevented the HR augmentation observed in the HS group (Fig 3B & 3C). During the light period a significant bradycardia was observed in HS/LK group (518±11 bpm vs. 484±7 bpm, Fig 3C). The same pattern was observed when animals were placed in the standard light/dark cycle: during the dark period, BP increased by 12 mmHg and 11 mmHg for HS and HS/LK respectively when HR increased by 54 bpm in the HS group and by 15 bpm only in the HS/LK cohort (data not shown).


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)

Effects of high-salt/normal potassium and high-salt/low potassium on mean blood pressure and heart rate in C57BL/6N mice.Mice were monitored with telemetry in the dark (A, B, C) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17), LS = low salt diet (n = 15), HS = high Na+/normal K+ diet (n = 8) and HS/LK = high Na+/low K+ diet (n = 6). 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.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0153472.g003: Effects of high-salt/normal potassium and high-salt/low potassium on mean blood pressure and heart rate in C57BL/6N mice.Mice were monitored with telemetry in the dark (A, B, C) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17), LS = low salt diet (n = 15), HS = high Na+/normal K+ diet (n = 8) and HS/LK = high Na+/low K+ diet (n = 6). 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: In C57BL/6N mice, when compared to normal potassium, the HS low potassium (HS/LK) intake did not affect the dark period BP increase that was superimposable in both groups (Fig 3A). Noteworthy, no statistically significant change in BP was observed during both HS/LK and HS diets during the light period (Fig 2C). Interestingly, HS/LK challenge prevented the HR augmentation observed in the HS group (Fig 3B & 3C). During the light period a significant bradycardia was observed in HS/LK group (518±11 bpm vs. 484±7 bpm, Fig 3C). The same pattern was observed when animals were placed in the standard light/dark cycle: during the dark period, BP increased by 12 mmHg and 11 mmHg for HS and HS/LK respectively when HR increased by 54 bpm in the HS group and by 15 bpm only in the HS/LK cohort (data not shown).

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