Postnatal changes in endothelin-1 binding in porcine pulmonary vessels and airways

Abstract

As the lung adapts to extrauterine life, the structure of the intrapulmonary arteries changes rapidly, in a similar manner in humans and pigs. The response to exogenous endothelin also changes in the perinatal porcine lung. Therefore we investigated the distribution and type of endothelin binding sites in the airways and vasculature of six to eight pig lungs in each of five age groups, from birth to adulthood. Using an in vitro autoradiographic technique, the distribution and density of 125I ET-1 binding was determined and characterized. At all ages, dense ET-1 binding was localized over the pulmonary and bronchial arteries and veins, bronchial smooth muscle, and the parenchymal region. Muscular pulmonary arteries and pulmonary veins had a higher density of binding than elastic arteries (P < 0.01). Between birth and adulthood, binding density decreased in extrapulmonary arteries (P < 0.05) and bronchial arteries (P < 0.01). The elastic intrapulmonary arteries showed a transient increase in binding density at 2 to 3 days of age (P < 0.05) and the muscular intra-pulmonary arteries showed one at 10 days of age (P < 0.05). The ETA antagonist BQ-123 and the ETB agonist sarafatoxin 6c were used to identify the receptor subtypes. Both subtypes were found on the medial smooth muscle cells at all ages. The majority of binding sites in the pulmonary arteries were ETA (75 to 92%). At 2 to 3 days of age only, ETB receptors were seen on the endothelium of the elastic pulmonary arteries, increasing the proportion of ETB receptors present. Thus we have demonstrated changes in endothelin receptors at a time when pulmonary vascular resistance falls. Their physiologic role remains to be elucidated.