一氧化氮合酶的抑制作用可减轻体内微循环中预激微血管的通透性。

Inhibition of nitric oxide synthase attenuates primed microvascular permeability in the in vivo microcirculation.

作者信息

Noel A A, Fallek S R, Hobson R W, Durán W N

机构信息

UMDNJ-New Jersey Medical School, Department of Surgery, Newark 07103-2714, USA.

出版信息

J Vasc Surg. 1995 Dec;22(6):661-9; discussion 669-70. doi: 10.1016/s0741-5214(95)70056-0.

DOI:10.1016/s0741-5214(95)70056-0

PMID:8523600

Abstract

PURPOSE

Changes in microvascular permeability play a critical role in the inflammatory sequence of tissue injury leading to leakage of proteins and subsequent edema. Primed responses induced by topical applications of platelet-activating factor (PAF) and histamine greatly increase microvascular permeability and mimic inflammation. We assessed the role of nitric oxide (NO) by use of 1-NG-monomethyl arginine (1-NMMA, a NO synthase inhibitor), on the primed microvascular permeability. We also explored the role of mast cells and a leukocyte adhesion complex by use of cromolyn sodium and 1B6 (a monoclonal antibody), respectively.

METHODS

Forty anesthetized hamsters were separated into five groups: group 1 (n = 5) received no intervention; group 2 (n = 5) received topical 10(-9) mol/L PAF and 10(-6) mol/L histamine at a 5-minute interval; group 3 (n = 5 at each dose) received PAF/histamine and 1-NMMA (at 10(-5) mol/L or 10(-6) mol/L); group 4 (n = 5 at each dose) received cromolyn sodium plus PAF/histamine; group 5 (n = 5) received 1B6 plus PAF/histamine. We examined the cheek pouch with intravital videomicroscopy under fluorescent epiillumination. We quantified microvascular permeability to fluorescein isothiocyanate-dextran 150 with computer-assisted images analysis on the basis of integrated optical intensity (IOI) measurements.

RESULTS

The mean (+/- SEM) IOI of the control group was 8.7 +/- 5.2, whereas the group primed with PAF and histamine was 62.4 +/- 10.8. The 1-NMMA (10(-5) mol/L and 10(-6) mol/L) abolished the changes in microvascular permeability (p < 0.05) yielding IOI values of 8.0 +/- 1.6 and 10.9 +/- 2.8, respectively. Cromolyn sodium and 1B6 did not significantly attenuate the primed response to PAF and histamine.

CONCLUSION

Inhibition of NO synthase attenuates primed macromolecular extravasation in vivo. Our results indicate that NO is involved in the primed reaction of PAF and histamine, causing increases in microvascular permeability. Our study suggests a role for NO in the microcirculatory changes observed in ischemia-reperfusion injury and shock.

摘要

目的

微血管通透性的改变在组织损伤的炎症反应序列中起关键作用，可导致蛋白质渗漏及随后的水肿。局部应用血小板活化因子（PAF）和组胺引发的反应可极大地增加微血管通透性并模拟炎症。我们通过使用1-NG-单甲基精氨酸（1-NMMA，一种一氧化氮合酶抑制剂）评估一氧化氮（NO）在引发的微血管通透性中的作用。我们还分别通过使用色甘酸钠和1B6（一种单克隆抗体）探究肥大细胞和白细胞黏附复合物的作用。

方法

将40只麻醉的仓鼠分为五组：第1组（n = 5）不接受干预；第2组（n = 5）每隔5分钟局部应用10⁻⁹ mol/L PAF和10⁻⁶ mol/L组胺；第3组（每个剂量n = 5）接受PAF/组胺和1-NMMA（10⁻⁵ mol/L或10⁻⁶ mol/L）；第4组（每个剂量n = 5）接受色甘酸钠加PAF/组胺；第5组（n = 5）接受1B6加PAF/组胺。在荧光落射照明下用活体视频显微镜检查颊囊。我们基于积分光强度（IOI）测量，通过计算机辅助图像分析对异硫氰酸荧光素-葡聚糖150的微血管通透性进行定量。

结果

对照组的平均（±SEM）IOI为8.7±5.2，而用PAF和组胺引发的组为62.4±10.8。1-NMMA（10⁻⁵ mol/L和10⁻⁶ mol/L）消除了微血管通透性的变化（p < 0.05），产生的IOI值分别为8.0±1.6和10.9±2.8。色甘酸钠和1B6并未显著减弱对PAF和组胺的引发反应。