Adrenomedullin: a new peptidergic regulator of the vascular function.

Adrenomedullin (AM) is a vasodilator peptide first identified in pheochromocytoma tissue, but endothelial cells and vascular smooth muscle cells actively secrete AM in addition to expressing AM receptors. AM dilates blood vessels through its direct action on the smooth muscle and the endothelial cell-mediated nitric oxide pathway. We have further demonstrated that AM is synthesized and secreted from macrophages, fibroblasts, cardiomyocytes and many other types of cells. AM secretion from these cells as well as the vascular wall cells are commonly stimulated with inflammatory cytokines and lipopolysaccharide. AM receptor is also widely distributed, and AM is shown to regulate production of inflammatory cytokines and cell growth. Based on these data, AM is deduced to be a multi-functional peptide participating in the regulation of vascular tone, inflammation and other physiologic events of the vasculature.