Abstract
Adrenomedullin (AM), a potent vasorelaxant peptide recently identified in extracts of pheochromocytoma, is actively secreted from vascular smooth muscle cells (VSMC). AM production in rat VSMC is potently stimulated by proinflammatory cytokines including TNF α, and glucocorticoids and many vasoactive substances have also been shown to alter AM synthesis. To study AM promoter function, we cloned the 5′-flanking region of the rat AM gene, and AM promoter function was assessed in rat VSMC stably transfected with a construct containing the cloned fragment. This 1.4 kb AM promoter region includes a number of putative transcriptional control elements. The promoter activity in VSMC was stimulated by TNF α and dexamethasone, and was suppressed by 8-bromo-cAMP and forskolin. These data indicate that transcriptional regulation is an important mechanism for AM production in VSMC.
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