IL-1beta alters hemodynamics in newborn intestine: role of endothelin.
IL-1beta alters hemodynamics in newborn intestine: role of endothelin.
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IL-1β 改变新生儿肠道的血流动力学：内皮素的作用。
DOI：
10.1152/ajpgi.00042.2006
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Nowicki,PhilipT
中科院分区：
文献类型：
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作者：
Nowicki,PhilipT
探讨IL-1β对新生儿肠道血流动力学的影响。IL-1β以剂量依赖的方式促进原代内皮细胞释放ET-1，同时减少内皮细胞上内皮素受体B型(ETB)的表达，增加血管平滑肌细胞上A型内皮素受体(ETA)的表达。IL-1β可增加内皮细胞内皮型一氧化氮合酶(ENOS)的表达，但不能增强eNOS的活性，这可通过乙酰胆碱或切应力使其释放到条件培养液中来证明。体外观察IL-1β对肠系膜动脉末端血流诱导的扩张作用。预先给予IL-1β(1 ng，4h)可显著减弱L/μ流速为100min和200min时的血管扩张反应。这种作用部分是通过内皮素ETA受体介导的；因此，用BQ610选择性阻断ETA受体几乎恢复了血流诱导的扩张。相反，外源性ET-1仅使直径-血流曲线下移，而不改变血管扩张对血流的反应百分率。然后在活体肠环上研究IL-1β对回肠氧合的影响。肠系膜动脉注入肠环上游的IL-1β可引起回肠血管收缩，并降低整个肠环的动-静脉氧分压差，从而使回肠氧合减少60%。BQ610可显著减弱这一效应。这些数据支持促炎细胞因子IL-1β与肠道循环内血管功能障碍之间的联系，至少部分是由ET系统介导的。
Studies were carried out to determine the effects of IL-1β on newborn intestinal hemodynamics. IL-1β increased the release of ET-1 by primary endothelial cells in a dose-dependent manner; as well, it reduced expression of the endothelin (ET) type B (ETB) receptor on endothelial cells and increased expression of the ET type A (ETA) receptor on vascular smooth muscle cells. IL-1β increased endothelial cell endothelial nitric oxide (NO) synthase (eNOS) expression but did not enhance eNOS activity as evidenced by release of NOxinto conditioned medium in response to acetylcholine or shear stress. The effects of IL-1β on flow-induced dilation were evaluated in terminal mesenteric arteries in vitro. Pretreatment with IL-1β (1 ng; 4 h) significantly attenuated vasodilation in response to flow rates of 100 and 200 μl/min. This effect was mediated, in part, by the endothelin ETAreceptor; thus selective blockade of ETAreceptors with BQ610 nearly restored flow-induced dilation. In contrast, exogenous ET-1 only shifted the diameter-flow curve downward without altering the percent vasodilation in response to flow. The effects of IL-1β on ileal oxygenation were then studied using in vivo gut loops. Intramesenteric artery infusion of IL-1β upstream of the gut loop caused ileal vasoconstriction and reduced the arterial-venous O2difference across the gut loop; consequently, it reduced ileal oxygenation by 60%. This effect was significantly attenuated by pretreatment with BQ610. These data support a linkage between the proinflammatory cytokine IL-1β and vascular dysfunction within the intestinal circulation, mediated, at least in part, by the ET system.