Kurose I, Kubes P, Wolf R, Anderson D C, Paulson J, Miyasaka M, Granger D N
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130-3932.
Circ Res. 1993 Jul;73(1):164-71. doi: 10.1161/01.res.73.1.164.
The mechanisms by which nitric oxide modulates microvascular albumin exchange were investigated by monitoring leukocyte-endothelial cell adhesion and fluorescein isothiocyanate-albumin leakage in rat mesenteric venules exposed to NG-nitro-L-arginine methyl ester (L-NAME). L-NAME elicited an initial rapid increase followed by a slower rate of albumin accumulation in the interstitial space. The initial phase of albumin leakage preceded the L-NAME-induced leukocyte adherence and emigration, whereas the magnitude of the albumin leakage observed in the later phase of L-NAME exposure was highly correlated with the number of adherent and emigrated leukocytes in the same segment of venule. Monoclonal antibodies (MAbs) directed against adhesion molecules CD11/CD18, ICAM-1, or P-selectin, but not a nonbinding MAb, attenuated the albumin leakage induced by L-NAME. WEB2086, a platelet activating factor antagonist, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) reduced the leukocyte adherence and emigration as well as the increased albumin leakage. Only 8-br-cGMP and the P-selectin MAb attenuated the platelet-leukocyte aggregation elicited by L-NAME. Phalloidin, which promotes endothelial junctional integrity, inhibited both the early and late phases of albumin leakage. Overall, these findings suggest that the increased albumin leakage observed in postcapillary venules after inhibition of nitric oxide production involves a mechanism that includes a role for cGMP, platelet activating factor, leukocyte-endothelial cell adhesion, and the endothelial cell cytoskeleton.
通过监测暴露于NG-硝基-L-精氨酸甲酯（L-NAME）的大鼠肠系膜小静脉中的白细胞-内皮细胞粘附以及异硫氰酸荧光素-白蛋白渗漏，研究了一氧化氮调节微血管白蛋白交换的机制。L-NAME引起间质空间中白蛋白积累的初始快速增加，随后速率减慢。白蛋白渗漏的初始阶段先于L-NAME诱导的白细胞粘附和移出，而在L-NAME暴露后期观察到的白蛋白渗漏程度与同一小静脉段中粘附和移出的白细胞数量高度相关。针对粘附分子CD11/CD18、ICAM-1或P-选择素的单克隆抗体（MAb），而非非结合性MAb，减弱了L-NAME诱导的白蛋白渗漏。血小板活化因子拮抗剂WEB2086和8-溴鸟苷3',5'-环一磷酸（8-br-cGMP）减少了白细胞粘附和移出以及增加的白蛋白渗漏。只有8-br-cGMP和P-选择素MAb减弱了L-NAME引起的血小板-白细胞聚集。促进内皮连接完整性的鬼笔环肽抑制了白蛋白渗漏的早期和晚期阶段。总体而言，这些发现表明，在抑制一氧化氮产生后，毛细血管后小静脉中观察到的白蛋白渗漏增加涉及一种机制，该机制包括cGMP、血小板活化因子、白细胞-内皮细胞粘附以及内皮细胞细胞骨架的作用。
