Localization of soluble guanylate cyclase (SGC) in pulmonary vasculature of fetal sheep

Activation of sGC by Nitric Oxide (NO) is essential for the pulmonary vasodilation that allows the establishment of gas exchange by the lungs at birth. The relative role of each segment of the pulmonary vasculature of the newborn in this activation of sGC is not known. Immunohistochemistry using the 64 antibody to the 82 kDA subunit of rat sGC (cross reacts with the sheep) was used to study differences along the pulmonary vasculature in fetal sheep. Specific staining was confined to vascular smooth muscle layers. At 1:6400 dilution, al! veins stained positively, whereas the largest positively stained artery associated with the terminal bronchiole was 200|.im. All vessels at the level of small terminal and respiratory bronchioles and alveolar ducts stained intensely positive. This pattern of differential staining between small and large pulmonary arteries supports previous physiologic studies in fetal sheep lung showing decreased sensitivity to NO in pulmonary arteries greater than 500 μm in diameter but sustained activity in pulmonary veins. Our data supports the role for sGC activation in the intraacinar arteries and veins of the newbron pulmonary circulation.