ENDOTHELIN PEPTIDES - BIOLOGICAL ACTIONS AND PATHOPHYSIOLOGICAL SIGNIFICANCE IN THE LUNG

Endothelins (ETs) are a family of novel regulatory peptides. Besides their effects on the cardiovascular system, which have been extensively described, several lines of evidence suggest an important role for ETs in regulating pulmonary functions. ETs are present in the pulmonary tissues, bronchoalveolar space and pulmonary circulation. Release of ETs from macrophages, endothelial and epithelial cells is modulated by a variety of chemical and physical stimuli and is regulated at the level of transcription or translation. Specific endothelin receptor have been identified in the airways as well as in the pulmonary vasculature. ETs are among the most potent bronchoconstrictors yet described. In the pulmonary circulation, ETs can elicit both vasodilation and vasoconstriction and can enhance vascular permeability. ETs could also modulate activation of inflammatory cells. Enhanced ET expression and/or production have been detected in asthma, certain pulmonary tumors, shock states associated with adult respiratory distress syndrome and pulmonary hypertension. These findings suggest that by regulating pulmonary vascular and airway tone, activation of inflammatory cells and cellular growth and/or differentiation, ETs may play an important role in pulmonary pathophysiology.