Pulmonary hypertension alters soluble guanylate cyclase activity and expression in pulmonary arteries isolated from fetal lambs

The nitric oxide (NO)-guanosine 3',5'-cyclic monophosphate (cGMP) signaling pathway plays an important role in the pulmonary vascular transition at bi rth. We studied pulmonary arteries and veins isolated from normal late-gest ation fetal lambs and from fetal lambs with persistent pulmonary hypertensi on (PPHN) following prenatal ligation of the ductus arteriosus. We addition ally used double immunolabeling and immunoblot analysis to determine relati ve vascular contents of endothelial nitric oxide synthase (NOS-III) and sol uble guanylate cyclase (sGC). Cyclic GMP content and sGC activity were significantly lower in arteries fr om hypertensive lambs than controls. A rank order for contents of both solu ble guanylate cyclase and NOS-III was observed by both immunolabeling and i mmunoblotting: Control vein = Hypertensive vein > Control artery > Hyperten sive artery. Our data demonstrate that the relative expression of sGC correlates well wi th the relative expression of NOS-III, and indicate the potential importanc e of soluble guanylate cyclase in the regulation of the perinatal pulmonary circulation. These data may help us understand vascular mechanisms produci ng PPHN, as well as patterns of response to exogenous NO. Pediatr Pulmonol. 2001; 31:97-105, (C) 2001 Wiley-Liss, Inc.