Ramírez M M, Quardt S M, Kim D, Oshiro H, Minnicozzi M, Durán W N
Department of Physiology, UMDNJ-New Jersey Medical School, Newark 07103-2714, USA.
Microvasc Res. 1995 Sep;50(2):223-34. doi: 10.1006/mvre.1995.1055.
Biochemical signaling determines the specific action of vasomediators in the control of microvascular permeability and tone. We tested the hypothesis that nitric oxide (NO) synthesis is involved in the biochemical signaling pathway of platelet activating factor (PAF). The cheek pouch of anesthetized male Syrian hamsters was used as a microvascular model. Vessel diameter [expressed as the ratio of the experimental to the control (e/c) diameter, with control diameter normalized to 1] and extravasation of FITC-dextran 150 by integrated optical intensity (IOI) were determined using intravital fluorescent microscopy and computer-assisted digital image analysis. N-Nitro-L-arginine methyl ester (L-NAME) at 10(-5) and 10(-6) M and N-nitro-L-mono-methyl arginine (L-NMMA) at 10(-4) and 10(-5) M were used as inhibitors of NO synthase (NOS). Acetylcholine (ACh) and bradykinin were used as indirect indices of NOS activation. L-NAME and L-NMMA attenuated both ACh and bradykinin vasodilatory effects as well as the bradykinin-induced increase in vascular permeability. Topical PAF (10(-7) M) caused vasoconstriction (mean +/- SEM e/c ratio = 0.3 +/- 0.1) and increased IOI from a normalized baseline of 0 to 67.4 +/- 12.8. Topical administration of L-NAME produced differential effects on the series-arranged arterioles but had no effect on postcapillary venular permeability. L-NMMA did not influence the basal arteriolar diameter, but at 10(-5) M it caused a small increase in permeability (IOI = 14.3 +/- 4.2). In the presence of NOS inhibitors, PAF caused a reduced arteriolar constriction (e/c ratio = 0.6 +/- 0.1) relative to PAF alone. Both NOS inhibitors reduced the PAF-stimulated increase in vasopermeability. At 10(-5) M L-NMMA, the PAF-stimulated IOI mean value was 26.1 +/- 5.2, while at 10(-4) M L-NMMA the PAF-stimulated IOI was 15.2 +/- 2.6 compared to 10(-7) M PAF (67.4 +/- 12.8). These results support our hypothesis that NO synthesis is a step in the biochemical signaling pathway of the postcapillary cellular responses to PAF.
生物化学信号传导决定了血管介质在控制微血管通透性和张力方面的特定作用。我们检验了一氧化氮（NO）合成参与血小板活化因子（PAF）生物化学信号传导途径的假说。将麻醉的雄性叙利亚仓鼠的颊囊用作微血管模型。使用活体荧光显微镜和计算机辅助数字图像分析，测定血管直径[表示为实验直径与对照（e/c）直径之比，对照直径标准化为1]以及通过积分光强度（IOI）测定的FITC-葡聚糖150的外渗情况。10^(-5) M和10^(-6) M的N-硝基-L-精氨酸甲酯（L-NAME）以及10^(-4) M和10^(-5) M的N-硝基-L-单甲基精氨酸（L-NMMA）用作一氧化氮合酶（NOS）的抑制剂。乙酰胆碱（ACh）和缓激肽用作NOS活化的间接指标。L-NAME和L-NMMA减弱了ACh和缓激肽的血管舒张作用以及缓激肽诱导的血管通透性增加。局部应用PAF（10^(-7) M）引起血管收缩（平均±SEM e/c比值 = 0.3 ± 0.1），并且使IOI从标准化基线0增加到67.4 ± 12.8。局部应用L-NAME对串联排列的小动脉产生不同影响，但对毛细血管后微静脉通透性无影响。L-NMMA不影响基础小动脉直径，但在10^(-5) M时它导致通透性略有增加（IOI = 14.3 ± 4.2）。在存在NOS抑制剂的情况下，相对于单独使用PAF，PAF引起的小动脉收缩减弱（e/c比值 = 0.6 ± 0.1）。两种NOS抑制剂均降低了PAF刺激引起的血管通透性增加。在10^(-5) M L-NMMA时，PAF刺激的IOI平均值为26.1 ± 5.2，而在10^(-4) M L-NMMA时，PAF刺激的IOI为15.2 ± 2.6，相比之下10^(-7) M PAF时为67.4 ± 12.8。这些结果支持我们的假说，即NO合成是毛细血管后细胞对PAF反应的生物化学信号传导途径中的一个步骤。
