Angiotensin II hypertension is attenuated in interleukin-6 knockout mice
Angiotensin II hypertension is attenuated in interleukin-6 knockout mice
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DOI：
10.1152/ajpheart.00708.2005
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发表时间：
2006-03-01
影响因子：
4.8
通讯作者：
Brands, MW
中科院分区：
文献类型：
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作者：
Lee, DL;Sturgis, LC;Brands, MW
在许多情况下，IL-6的血浆水平与高血压相关，并且ANG II已显示刺激各种细胞类型的IL-6产生。本研究检测了IL-6在介导高剂量ANG II和高盐饮食引起的高血压中的作用。雄性C57 BL 6和IL-6敲除（IL-6 KO）小鼠植入生物遥测装置，并置于代谢笼中，以测量平均动脉压（MAP）、心率（HR）、钠平衡和尿白蛋白排泄。对照期间，野生型（WT）和IL-6 KO小鼠的基线MAP平均值分别为114 +/- 1和109 +/- 1 mmHg，当小鼠接受高盐饮食（HS; 4% NaCl）时，MAP没有显著变化。ANG II（90 ng/min sc）引起两组MAP快速增加，WT和KO小鼠在第2天分别增加至141 +/- 9和141 +/- 4。在KO小鼠中MAP稳定在该水平（ANG II第14天为134 +/- 2 mmHg），但在WT小鼠中到第4天开始进一步增加，从ANG II第10天到第14天达到平均160 +/- 4 mmHg。ANG II第4天的尿白蛋白排泄在组间无差异（WT和KO小鼠为9.18 +/- 4.34和8.53 +/- 2.85 μ g/2天）。到第14天，WT小鼠的白蛋白排泄量几乎增加了4倍，但当14天后停止ANG II时，两组的MAP迅速下降至对照水平。因此，WT小鼠中ANG II高血压增加了30 mmHg，这表明IL-6对ANG II盐高血压有显著影响。此外，MAP的早期分离、白蛋白排泄数据和ANG II后MAP的快速恢复表明IL-6依赖性机制与肾损伤无关。
Plasma levels of IL-6 correlate with high blood pressure under many circumstances, and ANG II has been shown to stimulate IL-6 production from various cell types. This study tested the role of IL-6 in mediating the hypertension caused by high-dose ANG II and a high-salt diet. Male C57BL6 and IL-6 knockout (IL-6 KO) mice were implanted with biotelemetry devices and placed in metabolic cages to measure mean arterial pressure (MAP), heart rate (HR), sodium balance, and urinary albumin excretion. Baseline MAP during the control period averaged 114 +/- 1 and 109 +/- 1 mmHg for wild-type (WT) and IL-6 KO mice, respectively, and did not change significantly when the mice were placed on a high-salt diet (HS; 4% NaCl). ANG II ( 90 ng/min sc) caused a rapid increase in MAP in both groups, to 141 +/- 9 and 141 +/- 4 in WT and KO mice, respectively, on day 2. MAP plateaued at this level in KO mice (134 +/- 2 mmHg on day 14 of ANG II) but began to increase further in WT mice by day 4, reaching an average of 160 +/- 4 mmHg from days 10 to 14 of ANG II. Urinary albumin excretion on day 4 of ANG II was not different between groups (9.18 +/- 4.34 and 8.53 +/- 2.85 mu g/2 days for WT and KO mice). By day 14, albumin excretion was nearly fourfold greater in WT mice, but MAP dropped rapidly back to control levels in both groups when the ANG II was stopped after 14 days. Thus the similar to 30 mmHg greater ANG II hypertension in the WT mice suggests that IL-6 contributes significantly to ANG II-salt hypertension. In addition, the early separation in MAP, the albumin excretion data, and the rapid, post-ANG II recovery of MAP suggest an IL-6-dependent mechanism that is independent of renal injury.