Upregulation of ET-1 and its receptors and remodeling in small pulmonary veins under hypoxic conditions

Pulmonary veins show greater sensitivity to endothelin (ET)-1-induced vasoc onstriction than pulmonary arteries, and remodeling was observed in pulmona ry veins under hypoxic conditions. We examined, using an immunohistochemica l method, the expression of Big ET-1, ET-converting enzyme (ECE), and ETA a nd ETB receptors in rat pulmonary veins under normoxic and hypoxic conditio ns. In control rats, Big ET-1 and ECE were coexpressed in the intima and me dia of the pulmonary veins, with an even distribution along the axial pathw ay. ETA and ETB receptors were expressed in the pulmonary veins, with a pre dominant distribution in the proximal segments. The expression of Big ET-1 was more abundant in the pulmonary veins than in the pulmonary arteries. Af ter exposure to hypoxia for 7 or 14 days, the expression of Big ET-1, ECE, and ET receptors increased in small pulmonary veins. Increases in the media l thickness, wall thickness, and immunoreactivity for alpha -smooth muscle actin were also observed in the small pulmonary veins under hypoxic conditi ons. The upregulation of ET-1 and ET receptors in the small pulmonary veins is associated with vascular remodeling, which may lead to the development of hypoxic pulmonary hypertension.