Endothelin‐1, atrial natriuretic peptide and pathophysiology of pulmonary hypertension in porcine meconium aspiration

To evaluate the role of endothelin‐1 (ET‐1) and atrial natriuretic peptide (ANP) in the development of meconium aspiration‐induced pulmonary hypertension, plasma ET‐1 and ANP levels were measured serially for 6h after meconium instillation in juvenile pigs. Eleven 10‐week‐old, anaesthetized and catheterized pigs received intratracheally a bolus of 3 ml kg‐1 20% human meconium, and five of them were premedicated with 30 mg kg methylprednisolone i.v. Another six pigs served as controls and were given 3 ml kg‐1 sterile saline intratracheally. Meconium instillation resulted in an increase in plasma ET‐1 levels with a significant correlation to the simultaneously increasing 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 progressive pulmonary hypertension. ANP concentrations were higher in the meconium than in the control group throughout the study and further increased after steroid treatment with a good correlation to ET‐1 (r= 0:86). Thus, the postinjury rise in circulating vasoactive peptides, together with the pulmonary hypertensive response, and modulation of the peptide balance and pressor reaction by steroids, suggest a contributory role for ET‐1 and ANP in the development of pulmonary hypertension after meconium aspiration.