Endothelin-1-Like Immunoreactivity in Postobstructive Pulmonary Vasculopathy

Postobstructive pulmonary vasculopathy (POPV) is produced by chronic ligation of one pulmonary artery and results in bronchial collateral vessel proliferation and pulmonary arterial abnormalities. The role of endothelin-1 (ET-1), a potent vasoconstrictor peptide, was investigated in a canine model of POPV using radioimmunoassay and immunohistochemistry. The left main pulmonary artery of 9 dogs was ligated, and 3 months (n = 3) and 15 months (n = 6) later, ET-1 levels were measured by radioimmunoassay of plasma samples from left and right pulmonary arteries and veins. In addition, tissues from control and ligated lungs were fixed in Bouin's solution embedded in paraffin and stained with antiserum to ET-1. Plasma ET-1 levels distal to the ligation were not different from those of the control pulmonary artery (1.7 pg/ml in the ligated lungs vs. 1.4 pg/ml in the controls; NS). ET-1-like immunoreactivity was localized mainly to the epithelium in both control and ligated lungs, but the pulmonary arteries and the new bronchial vessels stained more intensely in the ligated lungs. The sections immunostained with ET-1 antiserum preabsorbed with synthetic ET-1 did not stain. These results suggest that ET-1 may play a role in the bronchial neovascularization and the pulmonary arterial thickening characteristic of POPV.