PRODUCTION AND SECRETION OF ADRENOMEDULLIN FROM VASCULAR SMOOTH-MUSCLE CELLS - AUGMENTED PRODUCTION BY TUMOR-NECROSIS-FACTOR-ALPHA

In this study, we demonstrate production and secretion of adrenomedull in (AM) from cultured vascular smooth muscle cells (VSMCs). In additio n to endothelial cells (ECs), we found immunoreactive (ir-) AM in cult ure media of rat and bovine VSMCs in the survey for AM-producing cells . Although the secretion level of ir-AM was at most 1/6 that of rat EC s, all the examined VSMCs were shown to produce AM. By gel filtration, reverse phase high-performance liquid chromatography, and biological characterization, ir-AM in the culture medium was identified to be rat AM of 50 residues. By RNA blot analysis, a positive band of AM mRNA w as detected in cultured VSMC at an intensity 3-4 fold higher than that in adrenal gland. Gene expression and production of AM were markedly augmented by tumor necrosis factor-alpha. Based on these data as well as the presence of AM specific receptors on VSMCs, AM secreted from VS MC is deduced to function as an autocrine or paracrine regulator in va scular cell communication. (C) 1994 Academic Press, Inc.