Endothelin-1 (ET-1) is a potent vasoconstrictor peptide which modulates basal pulmonary vascular resistance (PVR) in the normal ovine fetus and contributes to high PVR after chronic intrauterine pulmonary hypertension. Pulmonary hypertension complicates the course of the premature lamb with severe hyaline membrane disease (HMD); however, whether ET-1 plays a role in the pathophysiology of HMD is unknown. To test the hypothesis that ET-1 activity contributes to high PVR in the premature fetal lung with severe HMD, we studied the hemodynamic effects of a selective ET A receptor antagonist, BQ 123, in 7 fetal lambs (gestational age 125 days; 147 days = term). We placed catheters in the main pulmonary artery (PAP), aorta (AoP), and left atrium(LAP) to measure pressure and an ultrasonic flow transducer on the left pulmonary artery (LPA) to measure blood flow. After baseline measurements, animals were intubated, treated with surfactant (Infasurf), and mechanically ventilated (FiO2, 1.00). Animals were treated with either BQ 123 (1 mg/hour, n= 4) or saline (control; n = 3) in the MPA. One animal in the control group died at 4 hours. In comparison with controls, BQ 123 treated animals had lower PVR and improved LPA flow at 8 hours. (* = p<0.05 between groups)Table We conclude that selective ET A receptor blockade lowers PVR in experimental HMD. We speculate that ET-1 contributes to pulmonary hypertension in an ovine model of severe HMD.

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