title: How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains.
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.
authors.affiliation: Institut Clinique de la Souris, Institut de Génétique et de Biologie Moléculaire, Université de Strasbourg, Illkirch, France.
authors.forename: Roy
authors.initials: R
authors.lastname: Combe
authors.affiliation: Merck Research Laboratories, Kenilworth, New Jersey, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Mudgett
authors.affiliation: Institut Clinique de la Souris, Institut de Génétique et de Biologie Moléculaire, Université de Strasbourg, Illkirch, France.
authors.forename: Lahcen
authors.initials: L
authors.lastname: El Fertak
authors.affiliation: Institut Clinique de la Souris, Institut de Génétique et de Biologie Moléculaire, Université de Strasbourg, Illkirch, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Champy
authors.affiliation: Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Faculté de Médecine, Fédération de Médecine Translationnelle, Université et Centre Hospitalier Universitaire de Strasbourg, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Ayme-Dietrich
authors.affiliation: Institut Clinique de la Souris, Institut de Génétique et de Biologie Moléculaire, Université de Strasbourg, Illkirch, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Petit-Demoulière
authors.affiliation: Institut Clinique de la Souris, Institut de Génétique et de Biologie Moléculaire, Université de Strasbourg, Illkirch, France.
authors.forename: Tania
authors.initials: T
authors.lastname: Sorg
authors.affiliation: Institut Clinique de la Souris, Institut de Génétique et de Biologie Moléculaire, Université de Strasbourg, Illkirch, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Herault
authors.affiliation: Merck Research Laboratories, Kenilworth, New Jersey, United States of America.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Madwed
authors.affiliation: Institut Clinique de la Souris, Institut de Génétique et de Biologie Moléculaire, Université de Strasbourg, Illkirch, France.|Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Faculté de Médecine, Fédération de Médecine Translationnelle, Université et Centre Hospitalier Universitaire de Strasbourg, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Monassier
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D001795:Blood Pressure Determination / Q000379:methods; D002940:Circadian Rhythm / Q000502:physiology*; D004039:Diet, Sodium-Restricted; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL / Q000235:genetics; D011188:Potassium / Q000097:blood / Q000494:pharmacology / Q000652:urine; D012964:Sodium / Q000097:blood / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology*; D012982:Sodium, Dietary / Q000009:adverse effects / Q000494:pharmacology; D013686:Telemetry
chemical_list: D017673:Sodium Chloride, Dietary; D012982:Sodium, Dietary; D012964:Sodium; D011188:Potassium