Myoendothelial Junction Formation is Restricted in Pulmonary Arteries of Fetal Sheep

Abstract

Endothelial cell activation can hyperpolarize vascular myocytes, resulting in myocyte relaxation and vessel dilation. Direct communication by way of myoendothelial junctions (MEJ) made through the internal elastic lamina (IEL) contributes to vasodilatory responses. The function of the MEJ in pulmonary arteries is not completely understood and less is known regarding their function before birth. The fetal lung has little blood flow and endothelium‐dependent relaxation of pulmonary arteries is limited, which lead us to hypothesize that MEJs are underdeveloped in the fetal lung. This hypothesis was tested using laser scanning confocal microscopy techniques and viewing the IEL of pulmonary arteries from fetal and adult sheep. The IEL was viewed using autofluorescence, and MEJ's were visualized using cell mask red fluorescence. The number and size of pores in the IEL were quantified to index potential MEJ sites and this was compared to the number of MEJ sites that stained positive for cell membrane. Preliminary data suggests the size of each IEL pore, total pore area, and percentage of IEL holes with MEJs was greater in the adult. The restricted IEL pore and MEJ formation in the fetus could diminish MEJ –dependent myocyte hyperpolarization and resultant vasodilation. This could contribute to the high vascular resistance in the fetal pulmonary vasculature. Support from HHMI, NIH and NSF.