N-methyl-D-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets
N-methyl-D-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets
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DOI：
10.1152/ajpheart.00523.2001
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发表时间：
2002-04-01
影响因子：
4.8
通讯作者：
Bari, F
中科院分区：
文献类型：
--
作者：
Domoki, F;Perciaccante, JV;Bari, F
N-甲基-D-天冬氨酸（NMDA）与神经元一氧化氮（NO）的产生有关。然而，内皮因子或胶质细胞P-450环氧合酶产物可能发挥作用。我们测试了NMDA诱导的软脑膜血管舒张是否1）主要涉及NO从实质扩散到表面小动脉，2）涉及完整的内皮功能，3）涉及咪康唑敏感成分。在麻醉的小猪中使用闭合的颅窗活体显微镜测定小动脉直径。NMDA（10-100 μ M）在成对的小动脉中引起几乎相同的剂量依赖性扩张（r = 0.94，n = 15）。然而，与皮质表面的相邻切片相比，NMDA-而不是缓激肽（BK）-诱导的大静脉上的小动脉切片的扩张减少了31 +/- 1%（平均值+/- SE，P < 0.05，n = 4）。100 μM NMDA使脑脊液中NO代谢物的水平从3.7 +/- 1.0增加到5.3 +/- 1.2 μM（P < 0.05，n = 6）。颈动脉内注射佛波醇12，13-二丁酸酯致晕内皮细胞不影响NMDA诱导的血管舒张，但可使高碳酸血症和BK引起的血管反应减弱约70%（n = 7）。最后，咪康唑（n = 6，20 μ M）预处理和与NMDA的共同应用并没有改变血管对NMDA的反应。总之，NMDA似乎扩张软膜小动脉完全通过释放和扩散的NO从神经元的软膜表面在仔猪。
N-methyl-D-aspartate (NMDA) elicits pial arteriolar dilation that has been associated with neuronal nitric oxide (NO) production. However, endothelial factors or glial P-450 epoxygenase products may play a role. We tested whether NMDA-induced pial vasodilation 1) primarily involves NO diffusion from the parenchyma to the surface arterioles, 2) involves intact endothelial function, and 3) involves a miconazole-sensitive component. Arteriolar diameters were determined using closed cranial window-intravital microscopy in anesthetized piglets. NMDA (10-100 muM) elicited virtually identical dose-dependent dilations in paired arterioles (r = 0.94, n = 15). However, NMDA- but not bradykinin (BK)-induced dilations of arteriolar sections over large veins were reduced by 31 +/- 1% (means +/- SE, P < 0.05, n = 4) compared with adjacent sections on the cortical surface. Also, 100 μM NMDA increased cerebrospinal fluid levels of NO metabolites from 3.7 +/- 1.0 to 5.3 +/- 1.2 μM (P < 0.05, n = 6). Endothelial stunning by intracarotid injection of phorbol 12,13-dibutyrate did not affect NMDA- induced vasodilation but attenuated vascular responses to hypercapnia and BK by similar to70% (n = 7). Finally, miconazole (n = 6, 20 muM) pretreatment and coapplication with NMDA did not alter vascular responses to NMDA. In conclusion, NMDA appears to dilate pial arterioles exclusively through release and diffusion of NO from neurons to the pial surface in piglets.