Nonsteroidal anti-inflammatory drugs alter vasa recta diameter via pericytes.
Nonsteroidal anti-inflammatory drugs alter vasa recta diameter via pericytes.
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非甾体抗炎药通过周细胞改变直肠血管直径。
DOI：
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
C. Peppiatt
中科院分区：
文献类型：
--
作者：
T. Kennedy;C. Crawford;S. Wildman;C. Peppiatt
我们以前已经表明，已知直小血管周细胞在PGE 2存在下扩张直小血管毛细血管，并且当PGE 2的内源性产生被非选择性非甾体抗炎药（NSAID）吲哚美辛抑制时收缩直小血管毛细血管。在本研究中，我们使用了一个活的大鼠肾切片模型，以建立在这些初步观察，并提供新的数据，证明非选择性，环氧合酶-1-选择性，环氧合酶-2-选择性非甾体类抗炎药通过髓质周细胞引起直小血管直径的减少。记录原位直小血管的实时图像，并离线测量周细胞和非周细胞部位的直小血管直径。前列腺素E2和依前列醇（前列环素类似物）引起的扩张，特别是在周细胞的网站，和前列腺素E2显着衰减周细胞介导的收缩，内皮素-1和ANG II引起的直血管。NSAID（吲哚美辛> SC-560 >塞来昔布>美洛昔康）在周细胞部位引起的直血管毛细血管收缩显著大于非周细胞部位，吲哚美辛显著减弱PGE 2、依前列醇、缓激肽和S-亚硝基-N-乙酰基-L-青霉胺引起的周细胞介导的直血管舒张。此外，在用吲哚美辛灌注肾切片后，使用酶免疫测定法测量PGE 2的减少。此外，免疫组织化学技术被用来证明在髓质的EP受体的人口。总的来说，这些数据表明周细胞对PGE 2浓度的变化敏感，并且可能是NSAID相关肾损伤和/或进一步化合物相关肾小管损伤的主要机制。
We have previously shown that vasa recta pericytes are known to dilate vasa recta capillaries in the presence of PGE2 and contract vasa recta capillaries when endogenous production of PGE2 is inhibited by the nonselective nonsteroidal anti-inflammatory drug (NSAID) indomethacin. In the present study, we used a live rat kidney slice model to build on these initial observations and provide novel data that demonstrate that nonselective, cyclooxygenase-1-selective, and cyclooxygenase -2-selective NSAIDs act via medullary pericytes to elicit a reduction of vasa recta diameter. Real-time images of in situ vasa recta were recorded, and vasa recta diameters at pericyte and nonpericyte sites were measured offline. PGE2 and epoprostenol (a prostacyclin analog) evoked dilation of vasa recta specifically at pericyte sites, and PGE2 significantly attenuated pericyte-mediated constriction of vasa recta evoked by both endothelin-1 and ANG II. NSAIDs (indomethacin > SC-560 > celecoxib > meloxicam) evoked significantly greater constriction of vasa recta capillaries at pericyte sites than at nonpericyte sites, and indomethacin significantly attenuated the pericyte-mediated vasodilation of vasa recta evoked by PGE2, epoprostenol, bradykinin, and S-nitroso-N-acetyl-l-penicillamine. Moreover, a reduction in PGE2 was measured using an enzyme immune assay after superfusion of kidney slices with indomethacin. In addition, immunohistochemical techniques were used to demonstrate the population of EP receptors in the medulla. Collectively, these data demonstrate that pericytes are sensitive to changes in PGE2 concentration and may serve as the primary mechanism underlying NSAID-associated renal injury and/or further compound-associated tubular damage.
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DOI：
10.1172/jci117976
发表时间：
1995
期刊：
The Journal of clinical investigation.
影响因子：
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作者：
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期刊：
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2002-07
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DOI：
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2013
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American journal of physiology. Renal physiology
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降直血管对管腔压力的反应。
DOI：
10.1152/ajprenal.00394.2003
发表时间：
2004
期刊：
American journal of physiology. Renal physiology
影响因子：
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作者：
Zhang,Zhong;Pallone,ThomasL
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Pallone,ThomasL