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

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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.