Nonendothelial source of nitric oxide in arterioles but not in venules - Alternative source revealed in vivo by diaminofluorescein microfluorography
Nonendothelial source of nitric oxide in arterioles but not in venules - Alternative source revealed in vivo by diaminofluorescein microfluorography
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DOI：
10.1161/01.res.0000047529.26278.4d
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发表时间：
2002-12-13
影响因子：
20.1
通讯作者：
Suematsu, M
中科院分区：
文献类型：
--
作者：
Kashiwagi, S;Kajimura, M;Suematsu, M
本研究旨在观察在体微血管内NO生成的地形图分布。为此，在大鼠肠系膜上连续灌流对亚硝酸根离子(NO+)敏感的二氨基荧光素二乙酸酯，并通过激光共聚焦显微荧光术观察微血管内的荧光。两个主要部位的荧光强度随时间增加：微血管内皮细胞和肥大细胞。根据不同的一氧化氮合酶(NOS)抑制剂对局部应用的荧光敏感性判断，小动脉内皮细胞和肥大细胞的NO利用率主要由NOS1维持，而静脉内皮细胞的NO利用率则主要依赖于NOS3。在小静脉中，抑制剂引起的抑制反应的大小与白细胞黏附的密度呈正相关。NOS抑制剂显著减少但不能消除微动脉、毛细血管和小静脉中与NO+相关的荧光，提示这些微血管循环中存在其他来源的NO：NOS同工酶免疫组织化学显示，NOS1不仅存在于支配小动脉的神经纤维中，而且大量存在于肥大细胞中。体外培养的腹膜细胞激光流式细胞仪检测发现肥大细胞中NOS1大量表达。有趣的是，NOS3存在于毛细血管和小静脉的内皮细胞中，而在管径相近的远端小动脉中则不存在。这些结果表明，小动脉接受非内皮来源的NO，涉及神经末梢和肥大细胞中的NOS1，而小静脉依赖。内皮型一氧化氮合酶是其主要来源。此外，来自循环储存库的非酶来源的NO在不同类别的微血管中占相当大的比例。本文全文可在http://www.circresaha.org.上查阅
This study aimed to examine topographic distribution of microvascular NO generation in vivo. To this end, nitrosonium ion (NO+)-sensitive diaminofluorescein diacetate was superfused continuously on the rat mesentery and the fluorescence was visualized in the microvessels through laser confocal microfluorography. Two major sites exhibited a time-dependent elevation of the fluorescence: microvascular endothelia and mast cells. As judged by the fluorescence sensitivity to local application of different inhibitors of NO synthase (NOS), NO availability in arteriolar endothelium and mast cells appeared to be maintained mainly by NOS1, whereas that in venular endothelium greatly depends on NOS3. In venules, the magnitude of inhibitory responses elicited by the inhibitors was positively correlated with the density of leukocyte adhesion. NOS inhibitors significantly reduced, but did not eliminate, the NO+-associated fluorescence in arterioles, capillaries, and venules, suggesting alternative sources of NO in circulation for these microvessels: Immunohistochemistry for NOS isozymes revealed that NOS1 occurred not only in nerve fibers innervated to arterioles but also abundantly in mast cells. Laser flow cytometry of peritoneal cells in vitro revealed abundant expression of NOS1 in mast cells. Interestingly, NOS3 occurred in endothelia of capillaries and venules but not in those of distal arterioles with comparable diameters. These results suggest that the arterioles receive NO from nonendothelial origins involving NOS1 present in nerve terminals and mast cells, whereas venules depend. on the endothelial NOS as a major source. Furthermore, nonenzymatic sources of NO from circulating reservoirs constitute a notable fraction throughout different classes of microvessels. The full text of this article is available at http://www.circresaha.org.