INHIBITION OF NITRIC-OXIDE PRODUCTION - MECHANISMS OF VASCULAR ALBUMIN LEAKAGE
INHIBITION OF NITRIC-OXIDE PRODUCTION - MECHANISMS OF VASCULAR ALBUMIN LEAKAGE
复制标题
DOI：
10.1161/01.res.73.1.164
复制
发表时间：
1993-07-01
影响因子：
20.1
通讯作者：
GRANGER, DN
中科院分区：
文献类型：
--
作者：
KUROSE, I;KUBES, P;GRANGER, DN
本研究通过监测N（G）-硝基-L-精氨酸甲酯（L-NAME）对大鼠肠系膜微静脉白细胞-内皮细胞粘附和异硫氰酸荧光素-白蛋白渗漏的影响，探讨了一氧化氮调节微血管白蛋白交换的机制。L-NAME引起了一个初始的快速增加，然后是一个缓慢的速度白蛋白积累在间隙空间。白蛋白渗漏的初始阶段之前的L-NAME诱导的白细胞粘附和迁移，而在L-NAME暴露的后期阶段观察到的白蛋白渗漏的幅度是高度相关的粘附和迁移的白细胞在同一段小静脉的数量。针对粘附分子CD 11/CD 18、ICAM-1或P-选择素的单克隆抗体（MAb），而非结合性MAb，可减弱L-NAME诱导的白蛋白渗漏。血小板活化因子拮抗剂WEB 2086和8-溴环磷酸鸟苷（8-br-cGMP）可减少白细胞粘附和迁出，增加白蛋白渗漏。只有8-br-cGMP和P-选择素单克隆抗体能减弱L-NAME诱导的血小板-白细胞聚集。鬼笔环肽可促进内皮连接的完整性，抑制白蛋白渗漏的早期和晚期。总体而言，这些结果表明，在抑制一氧化氮产生后，在毛细血管后微静脉中观察到的白蛋白渗漏增加涉及一种机制，包括cGMP、血小板活化因子、白细胞-内皮细胞粘附和内皮细胞细胞骨架的作用。
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 N(G)-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.