Changes in pulmonary arterial smooth muscle structure with maturation and chronic hypoxia in sheep

Abstract

Chronic hypoxia (CH) can cause structural changes in the lung where the smooth muscle layer thickens due to myocyte hypertrophy and hyperplasia. CH compromises pulmonary arterial (PA) contractility and Ca2+‐signaling in the sheep fetus as well as the non‐pregnant ewe. Yet, the influence of CH on sheep PA and myocyte structure is unresolved, which is important as this relates to pulmonary pathologies. We therefore tested the hypothesis that CH thickens the smooth muscle layer and causes myocyte hypertrophy by evaluating the structure of PAs isolated from late‐gestational fetuses or adults maintained under normoxic conditions or exposed to CH by housing animals at 12,470 ft for ~ 110 days. To visualize smooth muscle cells, arterial segments were stained with anti‐α‐smooth muscle actin while nuclei were stained with DAPI. 3‐D images were made on a laser scanning confocal microscope by optical sample sectioning. The thickness of the smooth muscle layer was determined, as was myocyte and nuclear length, width, circumference, area and cell density. Fetal cells were smaller than adult and CH induced cellular hypertrophy in fetal and adult myocytes, although CH did not thicken the smooth muscle layer or alter cell density. Similarly, CH caused nuclear enlargement. Overall, these CH‐dependent changes in cell and nuclear morphometry are consistent with PA pathogenesis. Support from NSF, NIH, UM, LLUMC.