Mediators of the Plasma Extravasation Response to Silver Nitrate in the Rat Skin, Subplantar Region and Ankle Joint

Abstract

Abstract Plasma extravasation responses to silver nitrate (AgNO3), histamine, 5-hydroxytryptamine (5-HT), bradykinin and prostaglandin E1 (PGE1) in the abdominal skin, hindpaw ankle joint and subplantar region of rats have been investigated using the Evans blue dye leakage technique. All substances tested produced plasma extravasation and combination of low doses (5 × 10−10mol) of either histamine or bradykinin with PGE, (5 × 10−10mol) exhibited potentiation of responses of all regions. Responses to AgNO3 (1 × 10−6mol) were significantly reduced by the H1 receptor antagonist, mepyramine, only in the abdominal skin, but the H2 receptor antagonist metiamide reduced the responses at subplantar and ankle joint regions. Indomethacin significantly reduced the AgNO3 responses at the ankle joint only, but aprotinin reduced it at the other two regions. In rats pretreated with a combination of all antagonists the residual plasma extravasation response to AgNO3 was very small, indicating that the response could be almost totally accounted for by the combined actions of mast cell amines, kinins and prostanoids. The finding that prostanoids played a major role in the plasma extravasation response of the rat ankle joint to AgNO3 indicated that this model would be useful for the screening of non-steroidal anti-inflammatory drugs.