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 sites. In allergic asthma these sites are in the lung and the mediator substances cause airway obstruction by contracting smooth muscle and altering mucociliary function. Unlike histamine, slow-reacting substances (SRS) are 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 pure samples were not available for pharmacological studies. SRS isolated from both immunological and non-immunological reactions were identified as a combination of 2 related lipid substances, leukotriene C4 (LTC) and leukotriene D4 (LTD); it is now possible to use pure SRS (leukotrienes) in pharmacological studies of airway smooth muscle. LTC and LTD contract guinea pig tracheal and lung parenchymal strips but there is no evidence that these substances produce similar effects on human lung tissue. In vitro phamacological 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. All types of tissues contracted in a dose-dependent fashion to the leukotrienes, although these substances only function as partial agonists.