Newborn piglet lungs release endothelin-1: effect of α-thrombin and hypoxia

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Abstract
Endothelin-1 (ET-1) is a 21 amino acid vasoconstrictor peptide produced by endothelial cells, the expression of which is modulated by a variety of vasoconstrictors, vasodilators, and inflammatory mediators. Hypoxia has been shown to increase ET-1 expression and release in cultured endothelial cells from the systemic circulation, but reports are contradictory regarding the pulmonary circulation. In this study, the release of ET-1 and its cellular localization in the isolated perfused newborn piglet lung were examined under control conditions and after stimulation with hypoxia or α-thrombin (positive control). In the control condition, perfusion pressure remained stable during the study period, and a progressive increase in levels of immunoreactive ET-1 (irET-1) was noted. When α-thrombin was added to the perfusion fluid, a slow gradual increase in perfusion pressure was produced and the levels of irET-1 were significantly greater than those measured in the control preparations. Finally, hypoxia produced a significant increase in the perfusion pressure; however, the release of irET-1 did not differ significantly from the control, if anything, the net release across the lung was diminished. In all conditions, immunocytochemistry using antiserum to human–porcine ET-1 revealed the presence of high ET-1-like immunoreactivity in epithelial cells of bronchi, bronchioles, and terminal bronchioles. In addition, endothelial cells of large and medium-size pulmonary arteries were only moderately immunoreactive for ET-1. These findings indicate that the neonatal pig lung can produce and release ET-1, and that its release can be increased by certain stimuli like α-thrombin. On the other hand, acute hypoxia does not appear to be an important stimulus to ET-1 in the neonatal pulmonary circulation. Therefore, ET-1 is not likely to be involved in the hypoxic pulmonary vasoconstriction in the newborn piglet.Key words: neonatal pulmonary circulation, endothelium-derived constricting factor.

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