Slow-reacting substances (leukotrienes) contract human airway and pulmonary vascular smooth muscle in vitro

Abstract

During a type I allergic reaction histamine, slow-reacting substance of anaphylaxis (SRS-A) and other mediator substances are elaborated from specific tissue sites¹. In allergic asthma these sites are in the lung and the mediator substances cause airway obstruction by contracting smooth muscle and altering mucociliary function^2–4. Unlike histamine, slow-reacting substances (SRSs) have been assessed very little for their roles in obstructive airways disease. This has been partly due to the fact that their chemical nature was unknown until recently and thus pure samples were not available for pharmacological studies. However, SRSs isolated from both immunological and non-immunological reactions have been identified as a combination of two related lipid substances—leukotriene C₄ (LTC) and leukotriene D₄ (LTD)^5,6; thus it is now possible to use pure SRSs (leukotrienes) in pharmacological studies of airway smooth muscle. LTC and LTD have been shown to contract guinea pig tracheal and lung parenchymal strips⁵ but there is no evidence that these substances produce similar effects on human lung tissue. To clarify this, in vitro pharmacological studies were done to determine the actions of LTC and LTD on smooth muscle strips of human bronchus, pulmonary vein and artery, and lung parenchymal tissue containing smooth muscle components and pleura. As indicated in a preliminary report⁷, all four types of tissues contracted in a dose-dependent fashion to the leukotrienes, although these substances only function as partial agonists.