Kubes P
Department of Medical Physiology, University of Calgary, Alberta, Canada.
Am J Physiol. 1992 Jun;262(6 Pt 1):G1138-42. doi: 10.1152/ajpgi.1992.262.6.G1138.
The objective of this study was to assess whether inhibition of nitric oxide production leads to increased epithelial permeability in feline small intestine. Local intra-arterial infusion of the nitric oxide synthesis inhibitor NG-nitro-L-arginine-methyl ester (L-NAME; 0.025 mumol.ml-1.min-1) was performed in autoperfused segments of cat ileum for 90 min. An exogenous source of nitric oxide, sodium nitroprusside (SNP) was infused (0.025 mumol.ml-1.min-1) for the last 30 min of the 90-min L-NAME infusion. Epithelial permeability was quantitated by measuring blood-to-lumen clearance of 51Cr-labeled EDTA throughout the experiment. An increase of approximately sixfold in mucosal permeability was observed within 30 min of L-NAME infusion and this effect was completely reversed by infusion of either SNP or L-arginine (0.125 mumol.ml-1.min-1). NG-nitro-D-arginine-methyl ester (D-NAME) had no effect on mucosal permeability. The increase in epithelial permeability was sufficiently large that rhodamine-dextran (mol wt = 17,200) clearance from interstitium to lumen was increased. Pretreatment with IB4, a monoclonal antibody directed against the leukocyte adhesive glycoprotein complex (CD11/CD18) did not prevent the L-NAME-induced increase in epithelial permeability. These data suggest that inhibition of nitric oxide production leads to a reversible circulating leukocyte-independent increase in epithelial permeability.
本研究的目的是评估一氧化氮生成的抑制是否会导致猫小肠上皮通透性增加。在猫回肠的自体灌注节段中进行局部动脉内输注一氧化氮合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME；0.025 μmol·ml⁻¹·min⁻¹），持续90分钟。在90分钟L-NAME输注的最后30分钟内输注一氧化氮的外源性来源硝普钠（SNP，0.025 μmol·ml⁻¹·min⁻¹）。在整个实验过程中，通过测量51Cr标记的EDTA从血液到肠腔的清除率来定量上皮通透性。在L-NAME输注30分钟内观察到粘膜通透性增加约6倍，并且通过输注SNP或L-精氨酸（0.125 μmol·ml⁻¹·min⁻¹）可完全逆转这种效应。NG-硝基-D-精氨酸甲酯（D-NAME）对粘膜通透性没有影响。上皮通透性的增加足够大，以至于罗丹明-葡聚糖（分子量 = 17,200）从间质到肠腔的清除率增加。用针对白细胞粘附糖蛋白复合物（CD11/CD18）的单克隆抗体IB4预处理并不能阻止L-NAME诱导的上皮通透性增加。这些数据表明，一氧化氮生成的抑制导致上皮通透性可逆性增加，且不依赖循环白细胞。
