Acute Hypoxia Differentially Modifies Ca2+ Waves In Pulmonary Arterial Smooth Muscle Cells Of Intact Arteries From Fetal And Adult Sheep

Ca2+ signaling is important to pulmonary arterial (PA) contraction during acute hypoxia. To better understand Ca2+ signals under acute hypoxia in fetal and adult sheep, we performed confocal imaging of Fluo-4 loaded intact ovine PA Smooth Muscle Cells (PASMCs). Recordings were made in a controlled atmospheric chamber at ~37°C under normoxic conditions at ~300 m or during acute hypoxia, induced by exposing arteries to ~4% O2 for 30 min. Automated analysis procedures were used to examine Ca2+ waves to determine the magnitude, duration, and the number of regions of interest that had events at similar times (“friends”). We tested the hypothesis that acute hypoxia differentially modifies Ca2+ signaling in PASMCs of fetuses versus adults. Adult normoxic PASMC Ca2+ waves had lower AUC and shorter duration compared to fetuses, comparable amplitudes, but greater number of friends. In fetal PASMCs, acute hypoxia decreased Ca2+ wave duration, amplitude, and the area under the curve (AUC) but did not alter the number of friends. In adult sheep, acute hypoxia reduced Ca2+ wave amplitude and the number of friends, but did not impact wave duration or AUC. These results indicate that acute hypoxia modifies fetal and adult PASMC Ca2+ waves in unique ways. These differences in the Ca2+ responses may help define the resultant vasoreactivity in response to acute hypoxia in fetal and adult PASMCs. (Support from NIH and NSF)