Background: It has been suggested that, like ANP and BNP, high plasma levels of mature adrenomedullin (mAM) indirectly reflect the severity of heart failure or renal failure. However, the relationship between mAM levels and hemodynamics and cardiac function has not been examined in hemodialysis (HD) patients with coronary artery disease (CAD). The best marker, among mAM, ANP and BNP, for left-ventricular function in those patients is also unclear. Patients and Methods: Plasma levels of mAM, total AM (tAM), ANP and BNP were determined before HD in chronic HD patients with CAD (group 1; n = 17) and were compared with those of HD patients without cardiac disease (group 2; n = 22). We examined their relationship to hemodynamics and cardiac function in group 1 using data obtained by cardiac catheterization. Results: Plasma levels of ANP and BNP were significantly higher in group 1 than in group 2, but there was no significant difference in plasma levels of mAM and tAM between the two patient groups. Plasma levels of both mAM and tAM significantly correlated with right atrial pressure (RAP), and only plasma tAM levels correlated with pulmonary artery pressure (PAP) and pulmonary artery wedge pressure (PAWP). However, no correlations were found between levels of the two forms of AM and ejection fraction (EF). In contrast, plasma ANP and BNP levels significantly correlated with both PAP and PAWP, and also with EF, although they did not correlate with RAP. The correlation of PAP and PAWP with ANP and BNP levels was closer than that with tAM levels. The most significant correlation was between BNP levels and EF (r = –0.756, p < 0.0001). Conclusions: Our results suggest that the mAM level may be less useful than natriuretic peptide levels as a marker of cardiac function in HD patients with CAD, and that the BNP level might be the best indicator of left-ventricular function. In addition, cardiac disease such as CAD may have a minor impact on mAM levels compared to renal failure.

Keywords:
Atrial natriuretic peptide, Brain natriuretic peptide, Cardiac function, Coronary artery disease, Hemodynamics, Mature adrenomedullin
1.
Parfrey PS, Foley RN, Harnett JD, Kent GM, Murray D, Barre PE: Outcome and risk of ischemic heart disease in chronic uremia. Kidney Int 1996;49:1428–1434.
2.
Raine AEG, Erne P, Burgisser E, Muller FB, Bolli P, Burkart F, Buhler FR: Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med 1986;315:533–537.
3.
Morita E, Yasue H, Yoshimura M, Ogawa H, Jougasaki M, Matsumura T, Mukoyama M, Nakao K: Increased plasma levels of brain natriuretic peptide in patients with acute myocardial infarction. Circulation 1993;88:82–91.
4.
Saxenhofer H, Gnadinger MP, Weidmann P, Shaw S, Schohn D, Hess C, Uehlinger DE, Jahn H: Plasma levels and dialysance of atrial natriuretic peptide in terminal renal failure. Kidney Int 1987;32:554–561.
5.
Kohse KP, Feifel K, Mayer-Wehrstein R: Differential regulation of brain and atrial natriuretic peptides in hemodialysis patients. Clin Nephrol 1993;40:83–90.
6.
Ishizaka Y, Yamamoto Y, Fukunaga T, Yokota N, Kida O, Kitamura K, Kangawa K, Minamino N, Matsuo H, Eto T: Plasma concentration of human brain natriuretic peptide in patients on hemodialysis. Am J Kidney Dis 1994;24:461–472.
7.
Ishizaka Y, Yamamoto Y, Tanaka M, Kato F, Ishizaka Y, Yokota N, Kato J, Kitamura K, Eto T, Kangawa K, Minamino N, Matsuo H: Molecular forms of human brain natriuretic peptide (BNP) in plasma of patients on hemodialysis (HD). Clin Nephrol 1995;43:237–242.
8.
Osajima A, Okazaki M, Kato H, Anai H, Tsuda Y, Segawa K, Tanaka H, Tamura M, Takasugi M, Nakashima Y: Clinical significance of natriuretic peptides and cyclic GMP in hemodialysis patients with coronary artery disease. Am J Nephrol 2001;21:112–119.
9.
Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, Eto T: Adrenomedullin: A novel hypotensive peptide isolated from pheochromocytoma. Biochem Biophys Res Commun 1993;192:553–560.
10.
Kitamura K, Kato J, Kawamoto M, Tanaka M, Chino N, Kangawa K, Eto T: The intermediate form of glycine-extended adrenomedullin is the major circulating molecular form in human plasma. Biochem Biophys Res Commun 1998;244:551–555.
11.
Edwards RM, Trizna W, Aiyar N: Adrenomedullin: A new peptide involved in cardiorenal homeostasis? Exp Nephrol 1997;5:18–22.
12.
Suda T, Osajima A, Iwamoto M, Anai H, Tamura M, Kabashima N, Ota T, Watanabe Y, Kanegae K, Okazaki M, Nakashima Y: The mature form of adrenomedullin correlates with brain natriuretic peptide in plasma of chronic hemodialysis patients. Clin Nephrol 2002;57:444–457.
13.
Hirayama N, Kitamura K, Imamura T, Kato J, Koiwaya Y, Tsuji T, Kangawa K, Eto T: Molecular forms of circulating adrenomedullin in patients with congestive heart failure. J Endocrinol 1999;160:297–330.
14.
Massart PE, Hodeige D, Donckier J: Adrenomedullin: View on a novel vasodilatory peptide with natriuretic properties. Acta Cardiol 1996;51:259–269.
15.
Asakawa H, Nishikimi T, Suzuki T, Hara S, Tsubokou Y, Yagi H, Yabe A, Tsuchiya N, Horinaka S, Kangawa K, Matsuoka H: Elevation of two molecular forms of adrenomedullin in plasma and urine in patients with acute myocardial infarction treated with early coronary angioplasty. Clin Sci 2001;100:117–126.
16.
Nishikimi Saito Y, Kitamura K, Ishimutsu T, Eto T, Kangawa K, Matsuo H, Omae T, Matsuoka H: Increased plasma levels of adrenomedullin in patients with heart failure. J Am Coll Cardiol 1995;26:1424–1431.
17.
Yoshimura M, Yasue H, Okumura K, Ogawa H, Jougasaki M, Mukoyama M, Nakao K, Imura H: Different secretion patterns of atrial natriuretic peptide and brain natriuretic peptide in patients with congestive heart failure. Circulation 1993;87:464–469.
18.
Kobayashi K, Kitamura K, Hirayama N, Date H, Kashiwagi T, Ikushima I, Hanada Y, Nagatomo Y, Takenaga M, Ishikawa T, Imamura T, Koiwaya Y, Eto T: Increased plasma adrenomedullin in acute myocardial infarction. Am Heart J 1996;131:676–680.
19.
Nishikimi T, Nagata S, Sasaki T, Tomimoto S, Matsuoka H, Takishita S, Kitamura K, Miyata A, Matsuo H, Kangawa K: Plasma concentration of adrenomedullin correlates with the extent of pulmonary hypertension in patients with mitral stenosis. Heart 1997;78:390–395
20.
Yasue H, Obata K, Okumura K, Kurose M, Ogawa H, Matsuyama K, Jougasaki M, Saito Y, Nakao K, Imura H: Increased secretion of atrial natriuretic polypeptide from the left ventricle in patients with dilated cardiomyopathy. J Clin Invest 1989;83:46–51.
21.
Sugo S, Minamino N, Kangawa K, Miyamoto K, Kitamura K, Sakata J, Eto T, Matsuo H: Endothelial cells actively synthesize and secrete adrenomedullin. Biochem Biophys Res Commun 1994;201:1160–1166.
22.
Sugo S, Minamino N, Shoji H, Kangawa K, Kitamura K, Eto T, Matsuo H: Production and secretion of adrenomedullin from vascular smooth muscle cells: Augmented production by tumor necrosis factor-α. Biochem Biophys Res Commun 1994;203:719–726.
23.
Waldman SA, Rapoport RM, Murad F: Atrial natriuretic factor selectively activates particulate guanylate cyclase and elevates cyclic GMP in rat tissues. J Biol Chem 1984;259:14332–14334.
24.
Song D-L, Kohse KP, Murad F: Brain natriuretic factor: Augmentation of cellular GMP, activation of particulate guanylate cyclase and receptor binding. FEBS Lett 1989;232:125–129.
25.
Osajima A, Mutoh Y, Uezono Y, Kawamura M, Izumi F, Takasugi M, Kuroiwa A: Adrenomedullin increases cyclic AMP more potently than CGRP and amylin in rat tubular basolateral membranes. Life Sci 1995;57:457–462.
26.
Osajima A, Uezono Y, Tamura M, Kitamura K, Mutoh Y, Ueta Y, Kangawa K, Kawamura M, Eto T, Yamashita H, Izumi F, Takasugi M, Kuroiwa A: Adrenomedullin-sensitive receptors are preferentially expressed in cultured rat mesangial cells. Eur J Pharmacol 1996;315:319–325.
27.
Jougasaki M, Rodeheffer RJ, Redfield MM, Yamamoto K, Wei C-M, Mckinley LJ, Burnett JC Jr: Cardiac secretion of adrenomedullin in human heart failure. J Clin Invest 1996;97:2370–2376.
28.
Nishikimi T, Horio T, Sasaki T, Yoshihara F, Takishita S, Miyata A, Matsuo H, Kangawa K: Cardiac production and secretion of AM are increased in heart failure. Hypertension 1997;30:1369–1375.
29.
Ishihara T, Yokota S, Hisanaga S, Fujimoto S, Hirayama N, Koto J, Kitamura K, Eto T: Increased plasma levels of mature form of adrenomedullin in patients with chronic renal failure. Clin Nephrol 1999;52:119–123.
30.
Washimine H, Yamamoto Y, Kitamura K, Tanaka M, Ichiki Y, Kangawa K, Matsuo H, Eto T: Plasma concentration of human adrenomedullin in patients on hemodialysis. Clin Nephrol 1995;44:389–393.
31.
Letizia C, Mazzaferro S, Chicca S, Cerci S, Subioli S, Cinotti GA, D’Erasmo E: Changes in adrenomedullin plasma concentrations during haemodialysis in patients with chronic renal failure. Nephrol Dial Transplant 1999;14:519–520.
32.
Mallamaci F, Zoccali C, Parlongo S, Cutrupi S, Triperi G, Postorino M: Plasma adrenomedullin during acute changes in intravascular volume in hemodialysis patients. Kidney Int 1998;54:1697–1703.
33.
Toepfer M, Schlosshauer M, Sitter T, Burchardi C, Behr T, Schiffl H: Effects of hemodialysis on circulating adrenomedullin concentrations in patients with end-stage renal disease. Blood Purif 1998;16:269–274.
34.
Kato J, Kitamura K, Matsui E, Tanaka M, Ishizaka Y, Kita T, Kangawa K, Eto T: Plasma adrenomedullin and natriuretic peptides in patients with essential or malignant hypertension. Hypertens Res 1999;22:61–65.
© 2002 S. Karger AG, Basel
2002
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.