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      Plasma Adrenomedullin Levels in Patients on Hemodialysis

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          Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from human pheochromocytoma. In this study, we measured plasma AM concentrations in 54 patients on hemodialysis (HD) and examined the clinical significance. We also evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM levels. The average value of plasma AM at pre-HD (4.44 ± 0.16 fmol/ml) was significantly elevated compared with that in 44 healthy volunteers (1.31 ± 1.41 fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM concentrations at post-HD showed a negative correlation with MBP at post-HD and a negative correlation with the reduction rate of AM. Multiple regression analysis showed that age and MBP were independent factors associated with plasma AM at pre-HD and that MBP and reduction rate of AM were independent factors associated with plasma AM at post-HD. We investigated the differences between high-flux dialyzers (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high-flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did. In addition, in 3 patients on HD, plasma AM levels decreased significantly during isovolumic dialysis using a high-flux dialyzer, despite the fact that there were no significant changes in MBP and ANP. In conclusion, elevation in plasma AM level causes a fall in MBP in patients on HD, therefore, removal of AM by HD treatment using a high-flux dialyzer contributes to the stability of blood pressure during HD.

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          Most cited references 13

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          Endothelial cells actively synthesize and secrete adrenomedullin.

          This study demonstrates active production of adrenomedullin (AM) in cultured vascular endothelial cells (ECs). To identify the origin of plasma 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, porcine, 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 was almost comparable to that of endothelin-1. By gel filtration and reverse phase high performance liquid chromatography, ir-AM in the culture medium was shown to have chromatographic behavior indistinguishable from that of synthetic rat AM. By RNA blot analysis of rat tissue, the most highly positive band was detected in cultured ECs, at an intensity 20 to 40 fold higher than that in adrenal gland. Based on these data as well as the presence of AM specific receptor on VSMCs, AM secreted from ECs is deduced to act directly on VSMCs, regulating vascular tone.
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            Cloning and characterization of cDNA encoding a precursor for human adrenomedullin.

            Adrenomedullin is a novel hypotensive peptide recently isolated from human pheochromocytoma. Since a high concentration of immunoreactive adrenomedullin was found in pheochromocytoma tissue, the cDNA library of pheochromocytoma was constructed, and the cDNA clone encoding an adrenomedullin precursor was isolated and sequenced. The precursor for human adrenomedullin (human preproadrenomedullin) is 185 amino acids in length, including an adrenomedullin sequence. Proadrenomedullin (proAM) contains a unique twenty amino acid sequence followed by Gly-Lys-Arg in the N-terminal region. It is possible that a novel 20 residues peptide, termed "proadrenomedullin N-terminal 20 peptide" (proAM-N20) whose carboxy terminus may be Arg-NH2, is processed from proadrenomedullin. By RNA blot analysis, human adrenomedullin mRNA was found to be highly expressed in several tissues including adrenal medulla, ventricle, lung and kidney as well as pheochromocytoma.
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              Increased circulating adrenomedullin, a novel vasodilatory peptide, in sepsis

               Y Hirata (1996)

                Author and article information

                S. Karger AG
                24 August 2001
                : 89
                : 1
                : 20-25
                Department of Medicine III, Okayama University Medical School, Okayama, Japan
                46038 Nephron 2001;89:20–25
                © 2001 S. Karger AG, Basel

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                Page count
                Figures: 3, Tables: 2, References: 37, Pages: 6
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                Original Paper

                Cardiovascular Medicine, Nephrology

                Atrial natriuretic peptide, Hemodialysis, Adrenomedullin


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