Endothelins and pulmonary diseases.

Abstract

Endothelins (ETs) are expressed in several types of cell in human lung, including airway epithelial cells, pulmonary vascular endothelial cells, submucosal glands, and type II pneumocytes. There is evidence for increased expression of ET-1 in several pulmonary diseases, including asthma, fibrosing alveolitis, and pulmonary hypertension, suggesting that ET-1 may play a pathophysiological role. ET binding sites are widely distributed and are localized to airway and pulmonary vascular smooth muscle, fibroblasts, submucosal glands, and airway nerves, indicating that ETs may have widespread effects. ET-1 and ET-3 are potent constrictors of human airway smooth muscle via a direct effect on ET receptors in airway smooth muscle; these receptors are probably ETB receptors. ETs may have other effects on airway function, including constriction of bronchial vessels, increased plasma exudation, increased mucus secretion, airway smooth muscle hyperplasia, and possibly increased fibrogenesis; these effects may be mediated via ETA receptors. ET-1 is a potent constrictor of human pulmonary vessels, whereas ET-3 is less effective, suggesting a predominance of ETA receptors. Similarly, chemotaxis and mitogenesis of pulmonary vascular fibroblasts and smooth muscle are mediated via ETA receptors. These findings implicate ETs in various pulmonary diseases and suggest that ET antagonists may be useful in their treatment.