Production and clearance sites of two molecular forms of adrenomedullin in human plasma

Human adrenomedullin (AM) precursor is converted to glycine-extended AM (AM-Gly), an inactive intermediate form of AM. Subsequently, AM-Gly is converted to active mature AM (AM-m) by enzymatic amidation. A recent study showed that two molecular forms of adrenomedullin (AM) are present in human plasma. In this study we investigated the production and clearance sites of two molecular forms of adrenomedullin in humans. We measured plasma levels of AM-m and AM-Total (T) (AM-m+AM-Gly) by immunoradiometric assay and calculated plasma levels of AM-Gly in blood samples taken from various sites during cardiac catheterization in patients with ischemic heart disease. Plasma AM-m levels were significantly lower in left-sided sites after passing through pulmonary circulation than in right-sided sites, whereas there were no significant differences in AM-Gly levels between left-sided sites and right-sided sites. These results suggest that AM-m produced in many organs is released into veins and that the main clearance sites of AM-m are the lungs. Considering that AM preferentially dilates pulmonary vessels rather than systemic vessels, a possible role of this peptide is suggested in the regulation of pulmonary vascular tonus.