Soluble Guanylate Cyclase (sGC) is Decreased Within Pulmonary Arterial Smooth Muscle of Fetal Lambs with Experimentally-Induced Pulmonary Hypertension.• 1486

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) is characterized by structural and functional abnormalities of the pulmonary vasculature. Ligation of the ductus arteriosus in fetal lambs 10 days prior to delivery produces an animal model of PPHN. We previously reported that pulmonary arteries isolated from PPHN lambs demonstrate a blunted response to nitric oxide (NO). We now studied lungs isolated from fetal lambs (136 days gestation) using immunohistochemical staining techniques to determine differences in sGC distribution in the pulmonary vasculature between control lambs (n = 4) and lambs with PPHN after ductal ligation (n = 4). Following removal of lungs, barium gelatin was infused into the pulmonary arteries to distinguish small intra-alveolar arteries from post-capillary venules. A B4 primary antibody to the 82 kDa alpha subunit of rat sGC which cross-reacts with sheep sGC was used. Immunoreaction product was measured semiquantitatively using a three point scoring system. Structurally, pulmonary arteries from PPHN lambs displayed increased musculature of the medial layer and thickening of the adventitia. When compared to controls, sGC immunostaining in lambs with PPHN was significantly depressed at all levels of the arterial tree. The largest decrease in immunostaining compared to controls was seen at the level of the terminal bronchiole followed by arteries at the level of bronchi. In the venous tree, sGC immunostaining in PPHN lambs appeared unchanged from controls with the exception of postcapillary venules in which staining was significantly increased. These findings support our previous functional studies, and suggest there is decreased expression of sGC within vascular smooth muscle cells in this model of PPHN.