Combe Roy, Mudgett John, El Fertak Lahcen, Champy Marie-France, Ayme-Dietrich Estelle, Petit-Demoulière Benoit, Sorg Tania, Herault Yann, Madwed Jeffrey B, Monassier Laurent
Institut Clinique de la Souris, Institut de Génétique et de Biologie Moléculaire, Université de Strasbourg, Illkirch, France.
Merck Research Laboratories, Kenilworth, New Jersey, United States of America.
PLoS One. 2016 Apr 18;11(4):e0153472. doi: 10.1371/journal.pone.0153472. eCollection 2016.
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.
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).
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.
Therefore, to carry investigations on salt-induced hypertension in mice, chronic telemetry and studies in the active phase are essential prerequisites.
小鼠转基因技术为研究肾脏钠重吸收机制以及终末器官损伤提供了独特的机会。然而，了解小鼠背景以及实验条件对诸如血压等工程小鼠品系表型读数的影响是一项挑战。尽管在高盐饮食期间能够产生高钠和高氯血浆水平，但野生型背景品系和研究之间观察到的血压变化并不一致。
本研究旨在通过遥测连续记录接受不同钠和钾负荷饮食的小鼠的血压，并改变C57BL/6N和C57BL/6J小鼠品系的实验条件（正常盐饮食与低盐饮食与高盐/正常钾饮食与高盐/低钾饮食，标准光周期与改良光周期，无创尾袖带血压测量与遥测），以确定盐诱导高血压领域的指导原则。
在本研究中，我们发现，尽管C57BL/6N和C57BL/6J小鼠之间存在强烈的血压基础差异，但高盐/正常钾饮食仅在两个品系的活跃期（黑暗期）同等程度地增加血压和心率。另一方面，虽然钾水平对C57BL/6N小鼠的盐诱导高血压没有影响，但高盐/低钾饮食仅在C57BL/6J小鼠中放大了高盐挑战的作用。事实上，在这种情况下，即使与黑暗期相比血压升高较低，在光照期也能检测到盐诱导的高血压。最后，从方法学角度来看，光周期反转对这种昼夜血压表型没有影响，并且尾袖带法在检测盐挑战引起的血压表型方面比遥测法不那么敏感。
因此，要在小鼠中进行盐诱导高血压的研究，慢性遥测和活跃期研究是必不可少的先决条件。
