Endothelin-1 plasma concentration increases in the early phase of pulmonary hypertension development during respiratory distress syndrome:: a study in newborn lambs

Elevated plasma concentrations of endothelin-1 (ET-1) have been reported with pulmonary hypertension during respiratory distress syndrome (RDS). However, the exact role of ET-1 in the development of pulmonary hypertension during RDS is unclear. The relative time-course of changes in ET-1 concentrations and pulmonary artery pressure (P-ap) during RDS may give insight in the role of ET-1. Methods: ET-1 and P-ap changes were studied in an experimental model of RDS, induced by lung lavages in seven newborn lambs. Five other lambs served as controls. Results: Lung lavages induced a twofold increase of mean P-ap (from 15 to 34 mm Hg) that remained present throughout the 4-h study period. Along with the increased P-ap, ET-1 plasma concentration showed a significant increase 15 min after induction of RDS at all three sample locations (pulmonary artery 198%, aorta 181% and right atrium 195% compared to baseline). This increased concentration remained high at 1 and 4 h of RDS. In control animals, no significant changes in ET-1 concentrations were observed. Plotting ET-1 concentration values against mean P-ap, in RDS and control animals at all time points, a correlation was found between the severity of the pulmonary hypertension and ET-1 concentration. Conclusion: This experimental model of RDS shows that ET-I concentration increases concomitant with the development of pulmonary hypertension, from an early time point onward. More severe pulmonary hypertension is associated with higher ET-I concentrations, but whether ET-1 is a marker or a mediator of pulmonary hypertension remains as yet unsettled. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.