ABSTRACT
The initial pharmacological characterization of a potent vasoconstrictor peptide called endothelin (ET), released from porcine aortic endothelial cells, was reported by Yanagisawa and colleagues in 1988. Levels of immunoreactive ET in the lung are among the highest of any tissue. In human airways, immunoreactivity for ET-like peptides was detected in the vascular endothelium, airway epithelium and submucosal glands, and in macrophages. The ETs are good substrates for the catabolic enzyme neutral endopeptidase, which has similar affinity for each of the isopeptides. In some species, ET-1-induced airway smooth muscle contraction may also involve the release of secondary mediators in addition to its direct effects on airway smooth muscle, although the evidence is somewhat conflicting. Hydrostatic pulmonary edema occurs in response to ET-1 in rat and guinea pig isolated perfused lungs following increases in microvascular pressure, rather than as a result of an increase in microvascular permeability and plasma extravasation.
