Endothelin reactivity and receptor profile of pulmonary vessels in postobstructive pulmonary vasculopathy

Abstract

Chronic ligation of one pulmonary artery results in pulmonary vascular remodeling and bronchial angiogenesis, collectively known as postobstructive pulmonary vasculopathy (POPV). To determine whether the reactivity of pulmonary vessels to endothelins (ET) was altered in POPV and to explore potential mechanisms, we ligated the left main pulmonary artery of 18 rats. Four weeks later, using a lung explant technique, we compared POPV lungs with controls for contractile responses of intrapulmonary vessels to ET-1 and ET-3 and for relaxant responses to ET-1 and sodium nitroprusside (SNP) after precontraction with U-46619. Morphometric measurements were made on vessels studied pharmacologically. Competition receptor binding studies with 125I-labeled ET-1 and unlabeled ET-1 and BQ-123 were performed using membrane proteins of pulmonary vessels. We found, in arteries, that contractile responses to ET-1 and ET-3 were significantly increased and that relaxant responses to ET-1 but not to SNP were reduced; in veins, only relaxation to SNP was increased. Morphometry showed that arteries and veins in POPV had reduced diameters without altered muscle thickness. Receptor binding studies showed that the proportion of ETA receptors in arteries was significantly increased in POPV (66%) vs. controls (54%). We conclude that, in POPV, the increase in reactivity to ET-1 and ET-3 is primarily related to an augmented proportion of ETA receptors.