Prophylaxis with ketotifen in rats with portal hypertension: involvement of mast cell and eicosanoids.

Background: Since we have previously shown an increase of mast cells in the small bowel and in the mesenteric lymph nodes in the rats with prehepatic portal hypertension, it can be hypothesized that this essential inflammatory cell would be involved in the pathogeny of the splanchnic changes related to portal hypertension.

Methods: To verify this hypothesis, we first studied mast cell infiltration in the ileum and in the mesenteric lymph nodes in sham-operated male Wistar rats (n=12) and in short-term prehepatic portal hypertensive rats (n=12), and the serum levels of rat mast cell protease II (RMCP-II) by ELISA. In a second set of experiments ketotifen, a mast cell stabilizer drug, was administered to sham-operated (n=10) and portal hypertensive (n=12) rats 24 hours before the intervention and prostanoids (PGE2, PGI2, TXB2) and leukotrienes (LTC4, LTB4) were assayed by RIA, mast cell infiltration in the ileum and in the mesenteric lymph nodes and the serum levels of RMCP-II were also studied, to show its effectiveness to prevent the mesenteric alterations produced by the inflammatory mediators released by the mast cell.