The effect of synthetic leukotrienes on tracheal microvascular permeability

Abstract The effect of synthetic leukotrienes (LT) C 4 , D 4 and E 4 on the permeability of the airway microvasculature to plasma albumin was quantitatively evaluated using an in situ guinea pig tracheal model. Vascular permiability was measured as extravascular albumin content by employing 125 I-bovine serum albumin and, in order to correct for blood volume, 51 Cr-erythrocytes were used. Intratracheal injection of synthetic LTC 4 , LTD 4 and LTE 4 (0.1–1000 ng) produced dose-dependent increased in tracheal extravascular albumin content. The leukotrienes were approximately 100–1000 fold more potent than histamine, although histamine did produced a greater maximal increase in extravascular albumin than the leukotrienes. Methacholine did not increase extravascular albumin content. The microvascular permeability effect of LTD 4 was antagonized bu FPL 55712 but not by mepyraminel; conversely, the effect of histamine was antagonized by mepyramine and not by FPL 55712. Additionally, indomethacin did not alter the LTD 4 -induced increases in tracheal vascular permeability. These results suggest that the effect of LTD 4 on tracheal microvascular permeability is directly mediated and is not the indirect results of cholinergic stimulation, histamine release or de novo synthesis of cyclooxygenase products.