Involvements of NO and histamine in radiographic contrast medium-induced pulmonary dysfunction

尽管放射造影剂（RCM）越来越多地用于放射照相和磁共振成像，但与血管内注射RCM相关的不良反应，如类过敏反应和肺功能障碍偶尔会发生，并且尚未建立预防或有效治疗不良事件的方法。本研究旨在确定RCM诱发肺功能障碍的可能机制，并提出一种治疗或预防RCM严重不良反应的有效药物。研究结果如下：1。RCM引起肺肥大细胞脱颗粒，并由此释放组胺（HA），从而通过刺激H_1和H_2受体增加血管通透性。多种RCM刺激大鼠肺细胞HA释放，其中离子型RCM的作用比非离子型RCM更明显。阐明了离子rcm诱导肥大细胞释放HA的主要原因是细胞内环AMP含量的降低和细胞内Ca^<2+>的增加。ioxagate是一种离子RCM，通过刺激肥大细胞胰蛋白酶的释放诱导肺功能障碍。临床上可用的甲磺酸那莫他酯对预防或治疗血管内RCM注射的类过敏不良反应有潜在的作用。肥大细胞胰蛋白酶通过激活内皮蛋白酶活化受体-2，以依赖于磷脂酶C活性的方式损害内皮屏障功能。咔唑铬对预防rcm引起的急性肺部不良事件有潜在的作用。内皮屏障功能的稳定可能与咔唑色素的这种保护作用有关。

Although radiographic contrast media (RCM) are increasingly used for radiography and magnetic resonance imaging, undesirable actions associated with intravascular injection of RCM such as anaphylactoid adverse reactions and pulmonary dysfunction occur occasionally and no prevention or effective therapy for the adverse events has not been established. The present study was performed to determine the possible mechanisms underlying the RCM-induced pulmonary dysfunction and to propose a useful agent for the cure or prevention of servere adverse reaction to RCM. The research results as follows:1. RCM causes the degranulation of pulmonary mast cells and resultant release of histamine (HA) that in turn increases vascular permeability by stimulating H_1 and H_2 receptors.2. A variety of RCM stimulated HA release from rat pulmonary cells, in which the action of ionic RCM was more pronounced than that of non-ionic materials. It was clarified that the decrease in cellular cyclic AMP content and an increase in intracellular Ca^<2+> contributed largely to mast cell HA release induced by ionic RCM.3. Ioxaglate, an ionic RCM, induces pulmonary dysfunction by stimulating the release of mast cell tryptase. A clinically available nafamostat mesilate is potentially useful for the prevention or cure of anaphylactoid adverse reactions to the intravascular RCM injection.4. Mast cell tryptase impairs endothelial barrier function through activation of endothelial proteinase-activated receptor-2 in a manner dependent on the phospholipase C activity.5. Carbazochrome is a potentially useful for the prophylaxis of RCM-induced acute pulmonary adverse events. The stablization of endothelial barrier function may be associated with such a protective action of carbazochrome.