Abstract
We isolated vascular endothelial cells and smooth muscle cells from human donors of various ages and investigated their ability to secrete ET-1 and that to contract induced by ET-1. Expression of preproET-1 mRNA was enhanced with age of donor and secretion of ET-1 was also increased. Smooth muscle cells in culture contracted with changes of intracellular Ca2+ concentration as a response to ET-1 stimulation. Senescent cells less-responded to ET-1 stimulation than young cells. Senescent cells were suggested to have receptors for ET-1 fewer than young. Smooth muscle cells in aorta of the elderly were stained immunohistologically with anti-ET-1 antibody. When analyzed the culture medium of smooth muscle cells, it was found that smooth muscle cells synthesize and secrete ET-1. This suggests the possibility of autocrine action of ET-1 on smooth muscle cells. On the other hand, ET-1 receptor exists on the surface of endothelial cell itself, suggesting the possibility of cross-talk between endothelial cells and smooth muscle cells. Similar possibility can exist in heart: ET-1 stimulates the rhythmic heart-beat of cardiac myocytes and is produced by the cardiac myocyte itself under the condition of hypoxia.
