Domoki Ferenc, Perciaccante James V, Shimizu Katsuyoshi, Puskar Michelle, Busija David W, Bari Ferenc
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157-1010, USA.
Am J Physiol Heart Circ Physiol. 2002 Apr;282(4):H1404-9. doi: 10.1152/ajpheart.00523.2001.
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 microM) 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 microM NMDA increased cerebrospinal fluid levels of NO metabolites from 3.7 +/- 1.0 to 5.3 +/- 1.2 microM (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 approximately 70% (n = 7). Finally, miconazole (n = 6, 20 microM) 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.
N-甲基-D-天冬氨酸（NMDA）可引起软脑膜小动脉扩张，这与神经元型一氧化氮（NO）的产生有关。然而，内皮因子或胶质细胞P-450环氧合酶产物可能也发挥了作用。我们测试了NMDA诱导的软脑膜血管舒张是否：1）主要涉及NO从实质扩散至表面小动脉；2）涉及完整的内皮功能；3）涉及对咪康唑敏感的成分。使用闭合颅骨窗活体显微镜在麻醉的仔猪中测定小动脉直径。NMDA（10 - 100微摩尔）在配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，与皮质表面相邻节段相比，NMDA而非缓激肽（BK）诱导的大静脉上方小动脉节段的扩张减少了31±1%（平均值±标准误，P < 0.05，n = 4）。此外，100微摩尔的NMDA使脑脊液中NO代谢产物水平从3.7±1.0微摩尔升至5.3±1.2微摩尔（P < 0.05，n = 6）。通过颈内动脉注射佛波醇12,13 - 二丁酸使内皮失活并不影响NMDA诱导的血管舒张，但使血管对高碳酸血症和BK的反应减弱约70%（n = 7）。最后，咪康唑（n = 6，20微摩尔）预处理并与NMDA共同应用并未改变血管对NMDA的反应。总之，在仔猪中，NMDA似乎仅通过NO从神经元释放并扩散至软脑膜表面来使软脑膜小动脉扩张。
