Effects of exogeneous leukotrienes on the pulmonary circulation

This review illustrates the diverse effects of LTB4 and the peptidoleukotrienes (LTC4 and LTD4) on pulmonary hemodynamics and lung fluid balance. LTB4 had a lesser effect on pulmonary hemodynamics compared to the peptidoleukotrienes. The small increases in pulmonary artery pressure and pulmonary vascular resistance were the result of precapillary constriction associated with increases in effluent thromboxane concentration. On the other hand, peptidoleukotrienes resulted in marked increases in thromboxane concentrations, pulmonary artery pressure, pulmonary capillary pressure, and pulmonary vascular resistance. Increased thromboxane generation probably contributes to the noted hemodynamic alterations following peptidoleukotriene administration. Moreover, in the isolated perfused guinea pig lung, there was also a direct effect of LTD4 on pulmonary hemodynamics which was not blocked by cyclooxygenase inhibition. This latter, resistant vasoconstrictor response is analogous to the LTD4-mediated pulmonary vasoconstriction in some species which is not dependent on cyclooxygenase (Kadowitz et al., 1984). The primary site of vasoconstriction with LTD4 was in the postcapillary vessels in contrast to the LTB4 response. LTB4 increased lung vascular permeability directly (perhaps by a direct endothelial contracture) and may also contribute to increase in permeability via neutrophil activation. However, the neutrophil dependent permeability-increasing response could not be demonstrated in the isolated perfused guinea pig lung; thus, this response requires further study. In contrast, LTC4 and LTD4 had no effect on lung vascular permeability in the awake sheep, isolated perfused guinea pig lung, and the cultured bovine pulmonary endothelial monolayer system.