Increased Reactivity to Endothelin of Pulmonary Arteries in Long-term Post-obstructive Pulmonary Vasculopathy in Rats

Abstract

Post-obstructive pulmonary vasculopathy (POPV) describes the constellation of findings following chronic ligation of one pulmonary artery, including bronchial angiogenesis, pulmonary vasculopathy and increased vasoreactivity to pharmacologic agents. Previously, we found in rats with POPV of 28 days duration that maximal responses to endothelin-1 (ET-1) and ET-3 of pulmonary arteries but not veins were increased, and that relaxation of arteries to ET-1 was reduced, attributable to an elevated proportion of ETAover ETBreceptors. To determine the reactivity of pulmonary vessels and airways to ET in protracted POPV, we ligated the left main pulmonary artery of nine rats. Eleven months later, using a lung explant technique, we compared contractile responses of pulmonary vessels and airways to ET-1 and ET-3 in POPV lungs with controls. Morphometric measurements were made on the vessels, and immunoreactivity to ET-1 and endothelin converting enzyme (ECE-1) studied. We found contractile responses to ET-1 and ET-3 significantly increased in arteries, but not veins or airways. Morphometry showed arteries and veins had reduced diameters with muscle thickening only in veins. Expression of ET-1 and ET-3 in vascular endothelial cells and airway epithelial cells were not altered significantly. Our data suggest that protracted POPV selectively enhanced the contractility of pulmonary arteries to ET, and is not attributable to medial muscle thickening.