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      Plasma Levels of Proadrenomedullin N-Terminal 20 Peptide and Adrenomedullin in Patients Undergoing Hemodialysis

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          Background: Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide present in the precursor of adrenomedullin (AM), a vasodilative and natriuretic peptide. However, the profile of PAMP in hemodialyzed (HD) patients has not been determined. Methods: We measured plasma levels of PAMP, total AM (tAM) and a mature form of AM (mAM, the biologically active form) in HD patients (n = 31) and in normal controls (n = 21). Results: Plasma concentrations of PAMP before HD were significantly higher than those in controls (4.02 ± 0.24 vs. 1.64 ± 0.12 fmol/ml, p < 0.001) and decreased to the control level after HD (2.17 ± 0.18 vs. 1.64 ± 0.12 fmol/ml; NS). The plasma PAMP level before HD significantly correlated with weight gain during HD sessions (r = 0.41, p < 0.05), but not with predialysis blood pressure. The concentrations of mAM before and after HD were significantly higher than those in controls. The plasma mAM level before HD significantly correlated with weight gain during HD sessions, but not with predialysis blood pressure. The plasma level of PAMP did not correlate with that of mAM in HD patients. Conclusion: PAMP and AM may be involved in the regulation of blood volume in patients undergoing HD.

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          Most cited references 8

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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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            Plasma adrenomedullin during acute changes in intravascular volume in hemodialysis patients.

            Adrenomedullin, is a potent vasorelaxant that is highly expressed in the adrenal medulla, kidney, heart and lung. Since there is indirect evidence that hypervolemia enhances the release of this peptide, we measured plasma adrenomedullin in 9 uremic patients on chronic dialysis treatment and in 10 healthy subjects matched for age and gender. Measurements were performed in baseline conditions, after isotonic fluid subtraction (by isolated ultrafiltration) and during a 70 degrees tilt. Tilt was performed in volume-depleted state, that is, after isolated ultrafiltration (UF). In the control experiment patients underwent sham UF (UF = 0) followed by a period of supine resting identical to the one they had spent in tilted position in the active experiment. Adrenomedullin was measured on pre-extracted plasma samples (Sep-Pak C-18 cartridges) by a specific RIA for human adrenomedullin 1-52. The average plasma adrenomedullin was 2.6 times higher (P < 0.01) in uremic patients (103 +/- 8 pg/ml) than in healthy subjects (39 +/- 7 pg/ml). After fluid subtraction (-2.6 +/- 0.2 liter) adrenomedullin fell to 79. +/- 8 pg/ml (P = 0.02) but remained well above the upper limit of the 95% CI in normal subjects (52 pg/ml). There was no relationship between adrenomedullin and ANF changes. In the control experiment sham UF did not modify plasma adrenomedullin. Tilt did not significantly change plasma adrenomedullin either in dialysis patients or healthy subjects. Plasma adrenomedullin is markedly raised in uremic patients on dialysis, which confirms that the kidney has a major role in the clearance of this peptide. However, the fall in plasma adrenomedullin after isolated UF indicates that the plasma concentration of this peptide is influenced by the body fluid volume status. Whether or not adrenomedullin participates in the counter-regulatory response to fluid subtraction in uremic patients remains to be explored by specific antagonists of this substance.
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              Effect of adrenomedullin on renal hemodynamics and functions in dogs.

              In order to elucidate the role of adrenomedullin in the kidney, we investigated the effects of adrenomedullin on renal hemodynamics and urine formation in anesthetized dogs. Intrarenal arterial infusion of adrenomedullin (0.8, 4 and 20 elicited dose-dependent increases in renal blood flow (by 10, 26 and 37%, respectively) with no change in blood pressure or heart rate, indicating a renal vasodilatory action of adrenomedullin. The glomerular filtration rate did not increase with the lower two doses, but increased marginally by 9% at the highest dose. Infusion of adrenomedullin at the rates of 4 and 20 increased urine flow and the urinary excretion of sodium and potassium dose dependently. Arterial and renal venous plasma renin activity was unaffected by adrenomedullin. These findings indicate that adrenomedullin is a potent renal vasodilatory peptide with a diuretic action. Since the threshold for the renal vasodilatory action of adrenomedullin is close to its physiological concentration in human plasma, adrenomedullin may play an important role in the regulation of renal function.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                October 2003
                17 November 2004
                : 95
                : 2
                : c67-c72
                First Department of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan
                73670 Nephron Clin Pract 2003;95:c67–c72
                © 2003 S. Karger AG, Basel

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                Figures: 4, Tables: 1, References: 24, Pages: 1
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