Influence of hypoxia on endothelin-1 binding sites in neonatal porcine pulmonary vasculature

Exposure to chronic hypobaric hypoxia in the newborn piglet causes pulmonary hypertension and structural abnormalities in the intrapulmonary arteries that resemble those seen in babies with pulmonary hypertension of the newborn. To investigate whether the density and subtype of endothelin (ET) receptors in intrapulmonary arteries were altered by exposure to chronic hypobaric hypoxia (50.8 kPa) and changed on recovery, I-125-labeled ET-1 binding was studied using an in vitro autoradiographic technique on 67 piglets. Plasma ET was measured in 116 control, hypoxic, and recovery animals. In piglets exposed to hypoxia from birth, plasma ET was greater than normal for age (P < 0.05), and the binding density of ET-1 was increased in elastic arteries, muscular arteries, and veins due to an increase in the density of ETA binding (P < 0.05 for all vessel types). On recovery, plasma ET level became normal after 6 days. After 1 day of recovery, the binding density of ET-1 and ETA was normal in elastic arteries but was greater than normal in muscular arteries even after 6 days (P < 0.05). Exposure to hypoxia from 3 to 6 or from 14 to 17 days did not alter the plasma ET or the binding density in muscular arteries, but the density of binding of ET-1, ETA(A) and ETB in elastic pulmonary arteries decreased (P < 0.05). On recovery, it returned to normal by 6 days. In summary, the increases in plasma ET and ET-1 and ETA binding density suggest a role for ET in the pathogenesis of hypoxic pulmonary hypertension in the newborn period. An initial normal period of adaptation is protective.