Mayhan W G
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575.
Inflammation. 1992 Aug;16(4):295-305. doi: 10.1007/BF00917622.
The goal of this study was to determine the role of the synthesis and release of nitric oxide in modulating alterations in microvascular permeability of the hamster cheek pouch in response to adenosine 5'-diphosphate and bradykinin. We used intra-vital fluorescent microscopy to examine the permeability of the hamster cheek pouch to agonists before and following application of enzymatic inhibitors of nitric oxide, NG-monomethyl-L-arginine (L-NMMA; 0.01, 0.1, and 1.0 microM) and NW-nitro-L-arginine methyl ester (L-NAME; 0.01, 0.1, and 1.0 microM). Increases in permeability of the hamster cheek pouch were quantitated by the formation of microvascular leaky sites. ADP and bradykinin produced an increase in the number of venular leaky sites, and superfusion of L-NMMA and L-NAME significantly decreased ADP- and bradykinin-induced increases in microvascular permeability. To determine the specificity of nitric oxide blockade on microvascular permeability, we examined changes in permeability in response to adenosine, and examined the effects of D-NMMA on microvascular permeability. Adenosine-induced increases in permeability were not altered by treatment with L-NMMA, and D-NMMA did not inhibit ADP-induced increases in microvascular permeability. Thus, these findings suggest that production of nitric oxide, in response to application of ADP and bradykinin, has a role in modulating macromolecular permeability of the hamster cheek pouch in vivo.
本研究的目的是确定一氧化氮的合成与释放,在调节仓鼠颊囊微血管通透性因应5'-二磷酸腺苷和缓激肽而发生改变过程中所起的作用。我们利用活体荧光显微镜,在应用一氧化氮酶抑制剂Nω-甲基-L-精氨酸(L-NMMA;0.01、0.1和1.0微摩尔)和Nω-硝基-L-精氨酸甲酯(L-NAME;0.01、0.1和1.0微摩尔)之前和之后,检测仓鼠颊囊对激动剂的通透性。通过微血管渗漏部位的形成来定量仓鼠颊囊通透性的增加。ADP和缓激肽使小静脉渗漏部位数量增加,而L-NMMA和L-NAME的灌注显著降低了ADP和缓激肽诱导的微血管通透性增加。为了确定一氧化氮阻断对微血管通透性的特异性,我们检测了因应腺苷时通透性的变化,并检测了D-NMMA对微血管通透性的影响。L-NMMA处理未改变腺苷诱导的通透性增加,且D-NMMA未抑制ADP诱导的微血管通透性增加。因此,这些发现表明,因应ADP和缓激肽的应用而产生的一氧化氮,在体内调节仓鼠颊囊大分子通透性方面发挥作用。