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

Abstract

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(-1) 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.