Meconium aspiration is a severe neonatal respiratory disorder frequently complicated by pulmonary hypertension. To evaluate the role of endothelin-1(ET-1) and atrial natriuretic peptide (ANP) in this vascular disorder, plasma ET-1and ANP levels were measured serially for 6 hours after meconium instillation in juvenile pigs.

Eleven 10-week-old anesthetized and catheterized pigs received intratracheally a bolus of 3 ml/kg 20% human meconium, five of them were premedicated with 30 mg/kg methylprednisolone. Another six pigs served as saline controls. Ventilator settings were adjusted to avoid systemic hypoxemia and hypercarbia. Meconium aspiration resulted in a biphasic increase in plasma ET-1 level with a significant correlation to pulmonary vascular resistance(PVR) (r=0.72). Methylprednisolone had no effect on the early (0-1 h) ET-1 increase, but prevented significantly the second phase (1-6 h) rise with a concomitant attenuation of the pulmonary hypertensive response. ANP concentration was higher in the meconium than control group and further increased after steroid treatment with a good correlation to ET-1 (r=0.86).

Thus, the development of pulmonary hypertension after meconium aspiration is associated with a simultaneous rise in both ET-1 and ANP levels in plasma. Methylprednisolone pretreatment prevents the progressive elevation of both ET-1 and PVR with marked increase in ANP suggesting that these vasoactive peptides may contribute to the pathophysiology of meconium aspiration associated pulmonary hypertension.