Am. J. Respir. Cell Mol. Biol., Vol 12, No. 5, May 1995, 557-566.
Postnatal changes in endothelin-1 binding in porcine pulmonary vessels and airways
AA Hislop, YD Zhao, DR Springall, JM Polak and SG Haworth
Developmental Vascular Biology & Pharmacology Unit, Institute of Child Health, London, United Kingdom.
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.
