PROLONGED ENDOTHELIN A RECEPTOR BLOCKADE ATTENUATES CHRONIC INTRAUTERINE PULMONARY HYPERTENSION • 1994

Chronic intrauterine pulmonary hypertension (PH) from partial ligation of the ductus arteriosus causes failure of postnatal adaptation and structural remodeling in fetal lambs. To determine whether endothelin-1 (ET-1), a potent vasoconstrictor peptide, contributes to vascular changes in experimental PH, we studied the effects of BQ 123, a selective ET_A receptor antagonist, in PH. In 12 late gestation fetal lambs (126±3 days; 147 days, term) we ligated the ductus arteriosus, infused either BQ 123 (1 mg/day) or saline(control) in the pulmonary artery, and made serial measurements of fetal pulmonary artery pressure (PAP; mmHg). After 8 days of PH, 8 animals were delivered by cesarean section and ventilated with 100% oxygen. Animals were sacrificed for lung histology and cardiac weights of the right ventricle (RV) and left ventricle + septum (LV+S). BQ 123 lowered fetal PAP, enhanced vasodilation at delivery, and decreased right ventricular hypertrophy. BQ 123 treatment decreased medial hypertrophy of small pulmonary arteries by morphometric evaluation. We conclude that chronic blockade of the ET_A receptor lowers PAP in utero, improves pulmonary vasodilation at delivery, and attenuates right ventricular hypertrophy and structural change in chronic intrauterine PH. We speculate that endothelin is important in the pathogenesis of experimental perinatal pulmonary hypertension.Table

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