Increase in immunoreactivity to endothelin-1 in the mucosal vasculature and epithelium of the large intestine during chronic hypoxia.

Endothelin-1 is thought to play a role in the regulation of gastrointestinal function including its secretory role. This study investigated the localisation of endothelin-1 in the mucosa of the large intestine of normoxic and chronically hypoxic rats. Chronic hypoxia was produced by maintaining the animals in a hypoxic chamber. After animal perfusion/fixation, colonic segments from normoxic and hypoxic rats were investigated by the postembedding immunogold labelling procedure. In the microvasculature from normoxic (control) animals immunolabelling visualised as single particles was low and confined to the cytoplasm of endothelial cells. In the epithelium, immunolabelling was found mainly at the basal and apical regions of the cells. Chronic hypoxia for 10 d greatly enhanced the level of immunolabelling both in endothelial and epithelial cells of the mucosa. In endothelial cells clusters of gold particles were found in the cytoplasmic matrix and the subendothelium. Epithelial cells showed intense labelling, located mainly in the luminal/apical region within vacuole-like spaces and in the brush-border. In conclusion, hypoxia induces increase in immunoreactivity to endothelin-1 in gut endothelial and especially epithelial cells in the colonic mucosa.