Kurose I, Wolf R, Grisham M B, Granger D N
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
Am J Physiol. 1995 Jun;268(6 Pt 2):H2224-31. doi: 10.1152/ajpheart.1995.268.6.H2224.
The objective of this study was to determine whether an inhibitor of nitric oxide (NO) synthase (NG,NG'-dimethyl-L-arginine; L-DMA) that is produced by vascular endothelium elicits the inflammatory responses induced by synthetic analogues of L-arginine such as NG-nitro-L-arginine methyl ester (L-NAME). Leukocyte adherence and emigration, leukocyte-platelet aggregation, and albumin leakage were monitored in rat mesenteric venules exposed to different concentrations of either L-DMA or L-NAME. Increases in leukocyte adherence (7- to 9-fold) and emigration (3- to 5-fold), platelet-leukocyte aggregation, mast cell degranulation, and an enhanced albumin leakage (30-50%) were observed within 30 min after exposing the microvascular bed to either inhibitor; however, leukocyte emigration and albumin leakage responded more intensely to L-NAME than to L-DMA. The microvascular alterations and mast cell degranulation were attenuated by addition of L-arginine to the superfusate. These results suggest that the L-DMA is capable of eliciting an inflammatory response at concentrations detected in plasma under certain pathological conditions.
本研究的目的是确定血管内皮产生的一氧化氮（NO）合酶抑制剂（NG，NG'-二甲基-L-精氨酸；L-DMA）是否会引发由L-精氨酸合成类似物（如NG-硝基-L-精氨酸甲酯，L-NAME）诱导的炎症反应。在暴露于不同浓度L-DMA或L-NAME的大鼠肠系膜小静脉中监测白细胞黏附与迁移、白细胞-血小板聚集及白蛋白渗漏情况。将微血管床暴露于任何一种抑制剂后30分钟内，观察到白细胞黏附（增加7至9倍）和迁移（增加3至5倍）、血小板-白细胞聚集、肥大细胞脱颗粒以及白蛋白渗漏增强（30%至50%）；然而，白细胞迁移和白蛋白渗漏对L-NAME的反应比对L-DMA更强烈。向灌流液中添加L-精氨酸可减轻微血管改变和肥大细胞脱颗粒。这些结果表明，在某些病理条件下，L-DMA能够在血浆中检测到的浓度下引发炎症反应。
