Unraveling the Role and Complexities of Inflammation in Hypertension.
Unraveling the Role and Complexities of Inflammation in Hypertension.
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揭示炎症在高血压中的作用和复杂性。
DOI：
10.1161/hypertensionaha.117.09485
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Didion,SeanP
中科院分区：
文献类型：
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作者：
Didion,SeanP
IL-10缺乏对血压的二酮效应IL-10的损失与诱导型一氧化氮合酶和IL-6的血管表达增加有关，表明IL-10通常抑制这两种炎性分子的表达。7一个相关的问题是：如果促炎细胞因子水平升高（如本研究中观察到的IL-6和TNF-α升高），为什么IL-10缺乏时血压降低而不是升高？尽管在IL-10基因不存在的情况下与eNOS表达增加相关的机制很可能是复杂的并且尚未完全理解，但本身为抗炎分子的NO的增加可能用于限制炎性分子代替IL-10的表达。应该指出的是，NO对肾功能也有重要影响，例如，NO通过cGMP和PDE 2介导的Na+K+2Cl−协同转运蛋白活性降低而影响钠排泄，从而降低血压。11 Singh等人的研究结果具有启发性，因为他们认为，在缺乏IL-10的情况下，eNOS表达的上调可能作为肾脏的代偿性抗炎机制。除了确定IL-10缺乏本身对动脉压的影响外，作者还研究了IL-10缺乏对高盐和血管紧张素II引起的升压反应和肾损伤的影响。与先前的观察结果一致，高盐与野生型小鼠的血压变化无关。有些令人惊讶的是，IL-10缺乏也与用4%高盐饮食挑战的IL-10缺乏小鼠的血压变化无关。这些发现是新颖的，因为它们证明了IL-10缺乏与响应饮食钠增加的动脉压升高无关。
Didion Effects of IL-10 Deficiency on Blood Pressure 701 loss of IL-10 has been associated with increased vascular expression of inducible nitric oxide synthase and IL-6, suggesting that IL-10 normally suppresses the expression of these 2 inflammatory molecules. 7 A related question is: why is blood pressure reduced and not greater with IL-10 deficiency if levels of proinflammatory cytokines are elevated (such as the observed increase in IL-6 and TNF-α in the present study)? Although the mechanism (s) associated with increased eNOS expression in the absence of the IL-10 gene are most likely complex and not completely understood, it is possible that the increase in NO, which is itself an anti-inflammatory molecule, serves to limit expression of inflammatory molecules in lieu of IL-10. It should be pointed out that NO also has important effects on renal function, for example, NO influences sodium excretion via cGMP-and PDE2-mediated reductions in Na+K+2Cl− cotransporter activity resulting in blood pressure lowering. 11 The findings by Singh et al are provocative because they suggest that upregulation of eNOS expression may serve as a compensatory anti-inflammatory mechanism in the kidney in the absence of IL-10.In addition to determining the effects of IL-10 deficiency per se on arterial pressure, the authors also examined the effect of IL-10 deficiency on the pressor response and renal injury produced by high salt and angiotensin II. Consistent with previous observations, high salt was not associated with alterations in blood pressure in wild-type mice. Somewhat surprisingly, IL-10 deficiency was also not associated with alterations in blood pressure in IL-10–deficient mice challenged with a 4% high-salt diet. These findings are novel in that they demonstrate that IL-10 deficiency is not associated with increased arterial pressure in response to an increase in dietary sodium.