EFFECTS OF VASOACTIVE SUBSTANCES AND CAMP RELATED-COMPOUNDS ON ADRENOMEDULLIN PRODUCTION IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS

To elucidate the regulation mechanism of adrenomedullin (AM) productio n in blood vessels, we examined the effects of 30 substances on AM pro duction in cultured rat vascular smooth muscle cells (VSMCs). Forskoli n and and 8-bromo-cAMP suppressed production and gene transcription of AM. Since VSMC expresses AM receptors coupled with adenylate cyclase, AM production may be regulated by intracellular cAMP concentration. T hrombin, vasoactive intestinal polypeptide and interferon-gamma also i nhibited AM production, while angiotensin II, endothelin-1, bradykinin , substance P, adrenaline, phorbol ester and fetal calf serum stimulat ed AM production in VSMC. These results suggest that AM production is regulated by a variety of substances, indicating complex systems regul ating AM production.