Transcriptional regulation of adrenomedullin in rat vascular smooth musclecells

Adrenomedullin (AM), a potent vasorelaxant peptide recently identified in e xtracts of pheochromocytoma, is actively secreted from vascular smooth musc le cells (VSMC). AM production in rat VSMC is potently stimulated by proinf lammatory cytokines including TNF alpha, and glucocorticoids and many vasoa ctive substances have also been shown to alter AM synthesis. To study AM pr omoter function, we cloned the 5'-flanking region of the rat AM gene, and A M promoter function was assessed in rat VSMC stably transfected with a cons truct containing the cloned fragment. This 1.4 kb AM promoter region includ es a number of putative transcriptional control elements. The promoter acti vity in VSMC was stimulated by TNF alpha and dexamethasone, and was suppres sed by 8-bromo-cAMP and forskolin. These data indicate that transcriptional regulation is an important mechanism for AM production in VSMC. (C) 1999 E lsevier Science Ireland Ltd. All rights reserved.