INSERM U970, Paris - Centre de Recherche Cardiovasculaire; Université Paris Descartes, Paris, France.
Chronobiol Int. 2010 Jan;27(1):128-37. doi: 10.3109/07420520903398591.
A mutant mouse expressing a gain-of-function of the AT(1A) angiotensin II receptor was engineered to study the consequences of a constitutive activation of this receptor on blood pressure (BP). Cardiovascular rhythms and spontaneous cardiac baroreflex sensitivity (BRS) were evaluated using telemetric BP recordings of five transgenic (AT(1A)MUT) and five wild (AT(1A)WT) mice. The circadian rhythms were described with the Chronos-Fit program. The gain of the transfer function between systolic BP (SBP) and pulse intervals used to estimate the spontaneous BRS (ms/mmHg) was calculated in the low frequency (0.15-0.60 Hz) band. Transgenic AT(1A)MUT exhibited higher BP and heart rate (HR) levels compared to controls (SBP AT(1A)MUT 134.6 +/- 5.9 mmHg vs. AT(1A)WT 110.5 +/- 5.9; p < 0.05; HR AT(1A)MUT 531.0 +/- 14.9 vs. AT(1A)WT 454.8 +/- 5.4 beats/min; p = 0.001). Spontaneous BRS was diminished in transgenic mice (AT(1A)MUT 1.23 +/- 0.17 ms/mmHg vs. AT(1A)WT 1.91 +/- 0.18 ms/mmHg; p < 0.05). Motor activity did not differ between groups. These variables exhibited circadian changes, and the differences between the strains were maintained throughout the cycle. The highest values for BP, HR, and locomotor activity were observed at night. Spontaneous BRS varied in the opposite direction, with the lowest gain estimated when BP and HR were elevated (i.e., at night, when the animals were active). It is likely the BP elevation of the mutant mice results from the amplification of the effects of AngII at different sites. Future studies are necessary to explore whether AT(1A) receptor activation at the central nervous system level effectively contributed to the observed differences.
一种表达血管紧张素 II 受体（AT(1A)）功能获得性突变的小鼠被设计用来研究该受体的组成性激活对血压（BP）的影响。使用遥测血压记录，对五只转基因（AT(1A)MUT）和五只野生型（AT(1A)WT）小鼠进行心血管节律和自主心脏压力反射敏感性（BRS）评估。使用 Chronos-Fit 程序描述昼夜节律。用于估计低频（0.15-0.60 Hz）带中自主 BRS（ms/mmHg）的收缩压（SBP）和脉搏间隔之间传递函数的增益被计算出来。与对照组相比，转基因 AT(1A)MUT 表现出更高的血压和心率（HR）水平（SBP AT(1A)MUT 134.6 +/- 5.9 mmHg 与 AT(1A)WT 110.5 +/- 5.9 mmHg；p < 0.05；HR AT(1A)MUT 531.0 +/- 14.9 次/分钟与 AT(1A)WT 454.8 +/- 5.4 次/分钟；p = 0.001）。转基因小鼠的自主 BRS 降低（AT(1A)MUT 1.23 +/- 0.17 ms/mmHg 与 AT(1A)WT 1.91 +/- 0.18 ms/mmHg；p < 0.05）。两组之间的运动活动没有差异。这些变量表现出昼夜变化，并且在整个周期中，两组之间的差异得以维持。BP、HR 和运动活动的最高值出现在夜间。自主 BRS 呈相反方向变化，当 BP 和 HR 升高时（即夜间，动物活跃时），估计增益最低。突变型小鼠的 BP 升高可能是由于 AngII 在不同部位的作用放大所致。需要进一步研究以探讨中枢神经系统水平的 AT(1A)受体激活是否有效导致了观察到的差异。
