ENDOTHELIAL-CELLS ACTIVELY SYNTHESIZE AND SECRETE ADRENOMEDULLIN

This study demonstrates active production of adrenomedullin (AM) in cu ltured vascular endothelial cells (ECs). To identify the origin of pla sma AM and its functional relationship to vascular smooth muscle cells (VSMCs), we checked production of AM in a series of tissues and cell lines and found immunoreactive (ir-) AM in culture media of rat, porci ne, human and bovine ECs. Ir-AM was accumulated linearly for up to 48 hours in the culture medium of rat ECs, and the secretion rate of AM w as almost comparable to that of endothelin-1. By gel filtration and re verse phase high performance liquid chromatography, ir-AM in the cultu re medium was shown to have chromatographic behavior indistinguishable from that of synthetic rat AM. By RNA blot analysis of rat tissue, th e most highly positive band was detected in cultured ECs, at an intens ity 20 to 40 fold higher than that in adrenal gland. Based on these da ta as well as the presence of AM specific receptor on VSMCs, AM secret ed from ECs is deduced to act directly on VSMCs, regulating vascular t one. (C) 1994 Academic Press, Inc.