Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Am J Hypertens. 2010 May;23(5):481-7. doi: 10.1038/ajh.2010.12. Epub 2010 Feb 18.
Abnormal circadian variation of blood pressure (BP) increases cardiovascular risk. In this study, we examined the influence of angiotensin AT(1A) receptors on circadian BP variation, and specifically on its behavioral activity-related and -unrelated components.
BP and locomotor activity were recorded by radiotelemetry in AT(1A)-receptor knockout mice (AT(1A)(-/-)) and their wild-type controls (AT(1A)(+/+)) placed on a normal-salt diet (NSD) or high-salt diet (HSD, 3.1% Na).
The 24-h BP was lower in AT(1A)(-/-) than AT(1A)(+/+) mice on a NSD (92 +/- 2 and 118 +/- 2 mm Hg, respectively), whereas the day-night BP difference (DeltaDNBP) was similar between groups (11 +/- 2 and 12 +/- 1 mm Hg, respectively). HSD increased BP by 20 +/- 2 mm Hg and DeltaDNBP by 7 +/- 1 mm Hg in AT(1A)(-/-) mice, without affecting these parameters much in AT(1A)(+/+) mice. The DeltaDNBP increase in AT(1A)(-/-) mice was caused by nondipping BP during the inactive late-dark period. Conversely, BP rise associated with circadian behavioral activation during the early dark period was not altered by HSD in AT(1A)(-/-) mice. The BP change associated with spontaneous ultradian activity-inactivity bouts was also similar between strains on HSD as was the BP rise associated with induced (cage-switch) behavioral activity. Ganglionic or alpha(1)-adrenergic blockade decreased BP in both strains; HSD did not affect this response in AT(1A)(-/-), but abolished it in AT(1A)(+/+) mice.
AT(1A)-receptor deficiency, when combined with HSD, can increase circadian BP difference in mice. This increase is mediated principally by activity-unrelated factors, such as the nonsuppressibility of basal resting sympathetic tone by HSD, thus suggesting a form of salt-/volume-dependent hypertension.
血压（BP）的昼夜节律异常会增加心血管风险。在这项研究中，我们研究了血管紧张素 AT(1A)受体对昼夜 BP 变化的影响，特别是对其与行为活动相关和不相关的成分的影响。
通过无线电遥测术在 AT(1A)受体敲除小鼠（AT(1A)(-/-)）及其野生型对照（AT(1A)(+/+)）上记录 BP 和运动活动，这些小鼠分别置于正常盐饮食（NSD）或高盐饮食（HSD，3.1% Na）下。
在 NSD 下，AT(1A)(-/-)小鼠的 24 小时 BP 低于 AT(1A)(+/+)小鼠（分别为 92 +/- 2 和 118 +/- 2 mmHg），而两组之间的日夜间 BP 差异（DeltaDNBP）相似（分别为 11 +/- 2 和 12 +/- 1 mmHg）。HSD 使 AT(1A)(-/-)小鼠的 BP 升高 20 +/- 2 mmHg，DeltaDNBP 升高 7 +/- 1 mmHg，但对 AT(1A)(+/+)小鼠的这些参数影响不大。AT(1A)(-/-)小鼠的 DeltaDNBP 增加是由于在不活动的晚暗期非杓型 BP。相反，HSD 并没有改变 AT(1A)(-/-)小鼠在早期暗期与昼夜行为激活相关的 BP 升高。在 HSD 下，自发的超昼夜活动-不活动波之间的 BP 变化在两种品系之间也相似，与诱导（笼转换）行为活动相关的 BP 升高也是如此。神经节或 alpha(1)-肾上腺素能阻滞降低了两种品系的 BP；HSD 并没有影响 AT(1A)(-/-)小鼠的这种反应，但却消除了 AT(1A)(+/+)小鼠的这种反应。
当与 HSD 结合时，AT(1A)受体缺失可使小鼠的昼夜 BP 差异增加。这种增加主要是由与行为活动无关的因素介导的，例如 HSD 不能抑制基础静息交感神经张力，因此提示一种盐/容量依赖性高血压。
