Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron.
Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron.
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DOI：
10.1016/j.cmet.2015.11.013
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发表时间：
2016-02-09
期刊：
影响因子：
29
通讯作者：
Crowley SD
中科院分区：
文献类型：
--
作者：
Zhang J;Rudemiller NP;Patel MB;Karlovich NS;Wu M;McDonough AA;Griffiths R;Sparks MA;Jeffs AD;Crowley SD
高血压是世界范围内最普遍和最具灾难性的慢性疾病之一。虽然肾素血管紧张素系统（RAS）阻断在降低血压中的功效说明RAS在人类高血压中被广泛激活，但是RAS抑制预防或逆转高血压器官损伤的频繁失败突出了对抗RAS依赖性高血压的新疗法的需要。我们先前发现在RAS介导的高血压小鼠模型中，肾脏中巨噬细胞细胞因子IL-1水平升高。在这里，我们报告说，IL-1受体（IL-1 R1）的缺陷或封锁限制血压升高，在这个模型中，通过减轻钠重吸收NKCC 2协同转运蛋白在肾单位。在这种情况下，IL-1 R1激活阻止肾内髓样细胞成熟为Ly 6C + Ly 6 G −巨噬细胞，这些巨噬细胞产生一氧化氮，一种抑制NKCC 2活性的利钠激素。通过揭示先天免疫系统如何调节肾小管钠转运，这些实验将导致新的免疫调节抗高血压疗法。
Hypertension is among the most prevalent and catastrophic chronic diseases worldwide. While the efficacy of renin angiotensin system (RAS) blockade in lowering blood pressure illustrates that the RAS is broadly activated in human hypertension, the frequent failure of RAS inhibition to prevent or reverse hypertensive organ damage highlights the need for novel therapies to combat RAS-dependent hypertension. We previously discovered elevated levels of the macrophage cytokine IL-1 in the kidney in a murine model of RAS-mediated hypertension. Here we report that IL-1 receptor (IL-1R1) deficiency or blockade limits blood pressure elevation in this model by mitigating sodium reabsorption via the NKCC2 co-transporter in the nephron. In this setting, IL-1R1 activation prevents intra-renal myeloid cells from maturing into Ly6C+Ly6G− macrophages that elaborate nitric oxide, a natriuretic hormone that suppresses NKCC2 activity. By revealing how the innate immune system regulates tubular sodium transport, these experiments should lead to new immunomodulatory anti-hypertensive therapies.