Combined PDE-5 and ET
inhibition blocks pathological pulmonary vascular remodeling in SU-Hx rats. Images of a normoxic control lung (A), severely hypertensive lung in SU-Hx rats (B), and a lung from an SU-Hx animal treated with TAD/AMB for four weeks (C). Note that the SU-Hx lungs have marked muscularization of a pulmonary artery (PA, arrowheads), alongside a bronchiole (b), with several occlusive lesions located within the alveolar unit (arrows). TAD/AMB treatment led to normalization of pulmonary arteries, both at the bronchiolar level (b) as well as in intra-alveolar compartment (arrows), similar to the pulmonary artery morphology (arrows) seen in control lungs. High magnification images of the boxed areas are shown in the lower panels. In addition, in (B) the lower panel shows a classical plexiform-like lesion in a vehicle treated SU-Hx rat. This image was taken from a different slide. pl, visceral pleura; magnification bar =50 μm. Intimal occlusion (D) and medial thickening (E) in SU-Hx rats was reduced by TAD/AMB treatment. Values represent mean +/-SEM. *P < 0.05 vs. normoxia. †P < 0.05 vs. SU-Hx + vehicle. (F) Representative images of lung arterioles stained for von Willebrand factor (vWF; endothelial cell marker) and alpha smooth muscle actin (αSMA; smooth muscle cell marker). Images are overlaid with DAPI-stained nuclei; magnification bar =10 μm. Vessels from SU-Hx rats exhibited expansion of smooth muscle and endothelial cells, which was reduced by TAD/AMB treatment.