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Mechanisms for the dependency on angiotensin II hypertension on interleukin-6.

机译：白介素6对血管紧张素II高血压的依赖性机制。

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摘要

Angiotensin II (Ang II) is involved critically in the development and maintenance of hypertension in both human and animal models. Ang II also is known to stimulate interleukin 6 (IL-6) release, and a recent study by our laboratory demonstrated that Ang II hypertension was attenuated in IL-6 knockout (KO) mice. These data suggest that IL-6 mediates part of the hypertensive actions of Ang II. In addition, Ang II also stimulates production and release of aldosterone, which also has hypertensive actions. Ang II also stimulates the proinflammatory cytokine tumor necrosis factor-alpha (TNF-(alpha), which can stimulate IL-6 secretion. Therefore, the aim of this project was to determine whether the dependence of Ang II hypertension on II-6 is due to a direct link between Ang II and IL-6 or whether aldosterone and/or TNF-alpha are important intermediate factors. In separate studies, we determined whether mineralocorticoid hypertension is IL-6 dependent, the role of IL-6 bioactivity verses IL-6 plasma concentration, and the role of TNF-alpha in Ang II hypertension. Mineralocorticoid hypertension was induced by implanting a deoxycorticosterone acetate (DOCA) pellet (1 g/kg) subcutaneously and giving all animals a solution of 1% sodium chloride (NaCl) and 0.2% potassium chloride (KCl) to dink for a 14 day experimental period. DOCA-salt treatment increased the mean arterial pressure (MAP) similarly by ∼30 mm Hg in both the WT and IL-6 KO mice. However, DOCA-salt treatment did not increase plasma IL-6 concentration in wildtype (WT) mice nor did it increase IL-6 bioavailability using a bioassay on day 14 of treatment. There was, however, a transient increase in plasma IL-6 concentration and bioactivity on day 7 of DOCA-salt treatment in the WT mice. Treating WT mice with Ang II and the mineralocorticoid receptor antagonist, spironolactone, significantly attenuated the Ang II mediated increase in plasma IL-6 concentration on day 7 and day 14 of treatment. These data suggest that aldosterone might play a role in the initial increase in plasma IL-6 concentration during Ang II hypertension, but not the sustained increase. Similarly, Ang II increased MAP by -30 mm Hg in both the WT and TNF-alpha KO mice by day 14 of treatment. In WT mice Ang II treatment did not increase plasma levels of TNF-alpha. Ang II-induced hypertension is characterized by increased plasma levels of Ang II, aldosterone and IL-6 but not TNF-alpha. These data suggest that Ang II may work through an aldosterone but not TNF-alpha mediated mechanism to increase plasma IL-6 concentration in Ang II hypertension. However, these results suggest that the role of IL-6 in mediating Ang II hypertension may be independent of the interaction with aldosterone and TNF-alpha.
机译：血管紧张素II（Ang II）在人类和动物模型中均参与高血压的发展和维持。 Ang II还可以刺激白介素6（IL-6）释放，我们实验室的最新研究表明，Ang II高血压在IL-6基因敲除（KO）小鼠中得到了缓解。这些数据表明IL-6介导了Ang II的部分高血压作用。另外，Ang II也刺激醛固酮的产生和释放，醛固酮也具有高血压作用。血管紧张素Ⅱ还刺激促炎细胞因子肿瘤坏死因子-α（TNF-α），它可以刺激IL-6的分泌，因此，该项目的目的是确定血管紧张素Ⅱ对II-6的依赖性是否是由于与Ang II和IL-6之间的直接联系，或醛固酮和/或TNF-α是否是重要的中间因素。在单独的研究中，我们确定了盐皮质激素是否是IL-6依赖性的，IL-6的生物活性与IL- 6血浆浓度，以及TNF-α在Ang II高血压中的作用通过将醋酸脱氧皮质酮（DOCA）颗粒（1 g / kg）皮下植入并给所有动物提供1％氯化钠（NaCl）溶液诱导盐皮质激素高血压和0.2％的氯化钾（KCl）浸泡14天，DOCA盐处理对WT和IL-6 KO小鼠的平均动脉压（MAP）同样增加了约30 mm Hg。盐处理并没有增加血浆在治疗的第14天使用生物测定法检测野生型（WT）小鼠中IL-6的浓度，也不会增加IL-6的生物利用度。但是，在野生型小鼠中，DOCA-盐治疗的第7天，血浆IL-6浓度和生物活性出现短暂增加。在治疗的第7天和第14天，用Ang II和盐皮质激素受体拮抗剂螺内酯治疗WT小鼠可显着减弱Ang II介导的血浆IL-6浓度增加。这些数据表明，醛固酮可能在Ang II高血压期间血浆IL-6浓度的初始升高中起作用，但并非持续升高。类似地，在治疗的第14天，Ang II在WT和TNF-αKO小鼠中均使MAP增加-30 mm Hg。在野生型小鼠中，Ang II处理并未增加血浆中TNF-α的水平。血管紧张素Ⅱ诱导的高血压的特征是血浆血浆血管紧张素Ⅱ，醛固酮和IL-6水平升高，但不是TNF-α。这些数据表明，Ang II可能通过醛固酮起作用，但不通过TNF-α介导的机制来增加Ang II高血压患者的血浆IL-6浓度。然而，这些结果表明IL-6在介导Ang II高血压中的作用可能独立于与醛固酮和TNF-α的相互作用。

著录项

  • 作者

    Sturgis, LaShon C.;

  • 作者单位

    Medical College of Georgia.;

  • 授予单位 Medical College of Georgia.;
  • 学科 Biology Animal Physiology.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 147 p.
  • 总页数 147
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生理学;
  • 关键词

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