NEWBORN PIGLET LUNGS RELEASE ENDOTHELIN-1 - EFFECT OF ALPHA-THROMBIN AND HYPOXIA

Endothelin-1 (ET-1) is a 21 amino acid vasoconstrictor peptide produce d by endothelial cells, the expression of which is modulated by a vari ety of vasoconstrictors, vasodilators, and inflammatory mediators. Hyp oxia has been shown to increase ET-1 expression and release in culture d endothelial cells from the systemic circulation, but reports are con tradictory regarding the pulmonary circulation. In this study, the rel ease of ET-1 and its cellular localization in the isolated perfused ne wborn piglet lung were examined under control conditions and after sti mulation with hypoxia or alpha-thrombin (positive control). In the con trol condition, perfusion pressure remained stable during the study pe riod, and a progressive increase in levels of immunoreactive ET-1 (irE T-1) was noted. When alpha-thrombin was added to the perfusion fluid, a slow gradual increase in perfusion pressure was produced and the lev els of irET-1 were significantly greater than those measured in the co ntrol preparations. Finally, hypoxia produced a significant increase i n the perfusion pressure; however, the release of irET-1 did not diffe r 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-lik e immunoreactivity in epithelial cells of bronchi, bronchioles, and te rminal 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 re lease ET-1, and that its release can be increased by certain stimuli l ike alpha-thrombin. On the other hand, acute hypoxia does not appear t o be an important stimulus to ET-1 in the neonatal pulmonary circulati on. Therefore, ET-1 is not likely to be involved in the hypoxic pulmon ary vasoconstriction in the newborn piglet.