Effects of thiourea tolerance on plasma histamine, and lung vascular permeability

Adult male rats treated with a lethal edematogenic dose of thiourea (TU) (10.0 mg/kg, intraperitoneally) responded with significant elevations in plasma histamine, lung vascular permeability and 100% mortality over a subsequent 24-h period. When rats were pretreated with a small non-lethal dose of TU (0.5 mg/kg) and subsequently challenged with the lethal dose at 1, 4, 8, 16 and 32 days later, there was complete protection against death for at least 8 days and partial protection for an additional 24 days. This decrease in mortality correlated quite closely with reduced plasma histamine levels and diminished pulmonary vascular permeability. The results suggest that reduced exposure of the pulmonary vasculature to histamine may offer a partial explanation for tolerance to thiocarbamide compounds in the rat.