Skip to main content
Top
Published in: Endocrine 2/2015

01-03-2015 | Original Article

Pathophysiological functions of adrenomedullin and natriuretic peptides in patients with primary aldosteronism

Authors: Wei Hu, Pang-hu Zhou, Xiao-bin Zhang, Chang-geng Xu, Wei Wang

Published in: Endocrine | Issue 2/2015

Login to get access

Abstract

To measure the plasma concentrations of adrenomedullin (ADM),atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP), and investigate their pathophysiological functions in patients with primary aldosteronism (PA). Between June 2006 and December 2012, we recruited 25 patients with untreated PA, 30 patients with untreated low-renin essential hypertension (EH), and 35 healthy control subjects. The plasma concentrations of ADM, ANP, and BNP were measured in all the subjects. After 4 weeks of effective antihypertensive therapy with slow-release nifedipine, the three peptides were measured again in the PA and low-renin EH subjects. Unilateral laparoscopic adrenalectomy was performed in all the PA patients; 2 weeks after surgery, the three peptides were measured again. The PA patients had significantly higher plasma concentrations of ADM, ANP, and BNP than the low-renin EH and control subjects. The low-renin EH and control subjects significantly differed in the concentrations of the three peptides between low-renin EH and control subjects. ADM was the most important peptide associated with aldosterone or blood pressure in the PA patients. Plasma ADM concentration was not only correlated with plasma aldosterone concentrations, but also with systolic and diastolic blood pressures, and plasma ANP and BNP concentrations in the PA patients. By contrast, ADM concentration was not related to blood urea nitrogen levels, serum creatinine levels, and glomerular filtration rates. After antihypertensive treatment, the concentrations of the three peptides significantly decreased in the low-renin EH patients, but remained unchanged in the PA subjects. However, these concentrations significantly decreased 2 weeks after laparoscopic adrenalectomy in the PA subjects. ADM, ANP, and BNP possibly participate in the mechanisms counteracting further elevation of blood pressure or plasma volume expansion resulting from aldosterone hypersecretion in PA patients. An ADM/aldosterone local regulatory mechanism may be involved in regulating adrenal adenoma functions.
Literature
1.
2.
go back to reference B.M. Cheung, F. Tang, Adrenomedullin: exciting new horizons. Recent Pat. Endocr. Metab. Immune Drug Discov. 6(1), 4–17 (2012)CrossRefPubMed B.M. Cheung, F. Tang, Adrenomedullin: exciting new horizons. Recent Pat. Endocr. Metab. Immune Drug Discov. 6(1), 4–17 (2012)CrossRefPubMed
3.
go back to reference R. Di Iorio, E. Marinoni, D. Scavo, C. Letizia, E.V. Cosmi, Adrenomedullin in pregnancy. Lancet 349(9048), 328 (1997)CrossRefPubMed R. Di Iorio, E. Marinoni, D. Scavo, C. Letizia, E.V. Cosmi, Adrenomedullin in pregnancy. Lancet 349(9048), 328 (1997)CrossRefPubMed
4.
go back to reference J. Beltowski, A. Jamroz, Adrenomedullin: what do we know 10 years since its discovery? Pol. J. Pharmacol. 56(1), 5–27 (2004)PubMed J. Beltowski, A. Jamroz, Adrenomedullin: what do we know 10 years since its discovery? Pol. J. Pharmacol. 56(1), 5–27 (2004)PubMed
5.
go back to reference H. Nishida, T. Horio, Y. Suzuki, Y. Iwashima, K. Kamide, K. Kangawa, Y. Kawano, Plasma adrenomedullin as an independent predictor of future cardiovascular events in high-risk patients: comparison with C-reactive protein and adiponectin. Peptides 29(4), 599–605 (2008). doi:10.1016/j.peptides.2007.12.006 CrossRefPubMed H. Nishida, T. Horio, Y. Suzuki, Y. Iwashima, K. Kamide, K. Kangawa, Y. Kawano, Plasma adrenomedullin as an independent predictor of future cardiovascular events in high-risk patients: comparison with C-reactive protein and adiponectin. Peptides 29(4), 599–605 (2008). doi:10.​1016/​j.​peptides.​2007.​12.​006 CrossRefPubMed
8.
go back to reference E. TheodorakiArgyra, K. Theodoraki, P. Rellia, A. Marinis, D. Voros, G. Polymeneas, Atrial and brain natriuretic peptide changes in an experimental model of intra-abdominal hypertension. J. Surg. Res. 184(2), 937–943 (2013). doi:10.1016/j.jss.2013.03.036 CrossRef E. TheodorakiArgyra, K. Theodoraki, P. Rellia, A. Marinis, D. Voros, G. Polymeneas, Atrial and brain natriuretic peptide changes in an experimental model of intra-abdominal hypertension. J. Surg. Res. 184(2), 937–943 (2013). doi:10.​1016/​j.​jss.​2013.​03.​036 CrossRef
11.
go back to reference K. Kitamura, T. Eto, Adrenomedullin-physiological regulator of the cardiovascular system or biochemical curiosity? Curr. Opin. Nephrol. Hypertens. 6(1), 80–87 (1997)CrossRefPubMed K. Kitamura, T. Eto, Adrenomedullin-physiological regulator of the cardiovascular system or biochemical curiosity? Curr. Opin. Nephrol. Hypertens. 6(1), 80–87 (1997)CrossRefPubMed
12.
go back to reference E. Chollet-Dallon, C. Stoermann-Chopard, P.Y. Martin, Could cystatine C replace creatinine as a market of glomerular filtration rate? Revue medicale suisse 2(55), 582–585 (2006)PubMed E. Chollet-Dallon, C. Stoermann-Chopard, P.Y. Martin, Could cystatine C replace creatinine as a market of glomerular filtration rate? Revue medicale suisse 2(55), 582–585 (2006)PubMed
13.
go back to reference H. Ohta, T. Tsuji, S. Asai, S. Tanizaki, K. Sasakura, H. Teraoka, K. Kitamura, K. Kangawa, A simple immunoradiometric assay for measuring the entire molecules of adrenomedullin in human plasma. Clin. Chim. Acta 287(1–2), 131–143 (1999)CrossRefPubMed H. Ohta, T. Tsuji, S. Asai, S. Tanizaki, K. Sasakura, H. Teraoka, K. Kitamura, K. Kangawa, A simple immunoradiometric assay for measuring the entire molecules of adrenomedullin in human plasma. Clin. Chim. Acta 287(1–2), 131–143 (1999)CrossRefPubMed
14.
go back to reference H. Yasue, M. Yoshimura, H. Sumida, K. Kikuta, K. Kugiyama, M. Jougasaki, H. Ogawa, K. Okumura, M. Mukoyama, K. Nakao, Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 90(1), 195–203 (1994)CrossRefPubMed H. Yasue, M. Yoshimura, H. Sumida, K. Kikuta, K. Kugiyama, M. Jougasaki, H. Ogawa, K. Okumura, M. Mukoyama, K. Nakao, Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 90(1), 195–203 (1994)CrossRefPubMed
15.
go back to reference D.L. Hay, C.S. Walker, D.R. Poyner, Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: opportunities and challenges. Endocr. Relat. Cancer 18(1), C1–C14 (2011). doi:10.1677/erc-10-0244 CrossRefPubMed D.L. Hay, C.S. Walker, D.R. Poyner, Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: opportunities and challenges. Endocr. Relat. Cancer 18(1), C1–C14 (2011). doi:10.​1677/​erc-10-0244 CrossRefPubMed
16.
go back to reference T. Eto, J. Kato, K. Kitamura, Regulation of production and secretion of adrenomedullin in the cardiovascular system. Regul. Pept. 112(1–3), 61–69 (2003)CrossRefPubMed T. Eto, J. Kato, K. Kitamura, Regulation of production and secretion of adrenomedullin in the cardiovascular system. Regul. Pept. 112(1–3), 61–69 (2003)CrossRefPubMed
17.
go back to reference S. Kapas, A. Martinez, F. Cuttitta, J.P. Hinson, Local production and action of adrenomedullin in the rat adrenal zona glomerulosa. J. Endocrinol. 156(3), 477–484 (1998)CrossRefPubMed S. Kapas, A. Martinez, F. Cuttitta, J.P. Hinson, Local production and action of adrenomedullin in the rat adrenal zona glomerulosa. J. Endocrinol. 156(3), 477–484 (1998)CrossRefPubMed
18.
go back to reference G. Mazzocchi, G. Albertin, P.G. Andreis, G. Neri, L.K. Malendowicz, H.C. Champion, M. Bahcelioglu, P.J. Kadowitz, G.G. Nussdorfer, Distribution, functional role, and signaling mechanism of adrenomedullin receptors in the rat adrenal gland. Peptides 20(12), 1479–1487 (1999)CrossRefPubMed G. Mazzocchi, G. Albertin, P.G. Andreis, G. Neri, L.K. Malendowicz, H.C. Champion, M. Bahcelioglu, P.J. Kadowitz, G.G. Nussdorfer, Distribution, functional role, and signaling mechanism of adrenomedullin receptors in the rat adrenal gland. Peptides 20(12), 1479–1487 (1999)CrossRefPubMed
19.
go back to reference M. Forneris, L. Gottardo, G. Albertin, L.K. Malendowicz, G.G. Nussdorfer, Expression and function of adrenomedullin and its receptors in Conn’s adenoma cells. Int. J. Mol. Med. 8(6), 675–679 (2001)PubMed M. Forneris, L. Gottardo, G. Albertin, L.K. Malendowicz, G.G. Nussdorfer, Expression and function of adrenomedullin and its receptors in Conn’s adenoma cells. Int. J. Mol. Med. 8(6), 675–679 (2001)PubMed
20.
go back to reference T. Kita, M. Tokashiki, K. Kitamura, Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in patients with primary aldosteronism. Hypertens. Res. 33(4), 374–379 (2010). doi:10.1038/hr.2010.8 CrossRefPubMed T. Kita, M. Tokashiki, K. Kitamura, Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in patients with primary aldosteronism. Hypertens. Res. 33(4), 374–379 (2010). doi:10.​1038/​hr.​2010.​8 CrossRefPubMed
21.
go back to reference D.G. Kong, H. Gao, Y.Q. Lu, X.W. Qi, L.L. Ma, X.Q. Kong, D.K. Yao, L.X. Wang, Anxiety disorders are associated with increased plasma adrenomedullin level and left ventricular hypertrophy in patients with hypertension,Clin. Exp. Hypertens. (New York, NY, 1993) (2013). doi:10.3109/10641963.2013.783049 D.G. Kong, H. Gao, Y.Q. Lu, X.W. Qi, L.L. Ma, X.Q. Kong, D.K. Yao, L.X. Wang, Anxiety disorders are associated with increased plasma adrenomedullin level and left ventricular hypertrophy in patients with hypertension,Clin. Exp. Hypertens. (New York, NY, 1993) (2013). doi:10.​3109/​10641963.​2013.​783049
23.
go back to reference A. Grzywa-Celinska, R. Celinski, K. Kwasniewska, M. Dyczko, A. Prystupa, J. Mosiewicz, The usefulness of natriuretic peptides measurements in the diagnostics of chosen cardiovascular diseases. Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 34(202), 232–234 (2013) A. Grzywa-Celinska, R. Celinski, K. Kwasniewska, M. Dyczko, A. Prystupa, J. Mosiewicz, The usefulness of natriuretic peptides measurements in the diagnostics of chosen cardiovascular diseases. Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 34(202), 232–234 (2013)
24.
go back to reference R. Irzmanski, L. Pawlicki, M. Charlusz, J. Kowalski, Concentration of natriuretic peptides in patients suffering from idiopathic arterial hypertension and left ventricular diastolic dysfunction confirmed by echocardiography. Clin. Exp. Hypertens. (New York, NY, 1993) 34(7), 530–540 (2012). doi:10.3109/10641963.2012.702831 CrossRef R. Irzmanski, L. Pawlicki, M. Charlusz, J. Kowalski, Concentration of natriuretic peptides in patients suffering from idiopathic arterial hypertension and left ventricular diastolic dysfunction confirmed by echocardiography. Clin. Exp. Hypertens. (New York, NY, 1993) 34(7), 530–540 (2012). doi:10.​3109/​10641963.​2012.​702831 CrossRef
25.
go back to reference F. Pizzolo, F. Zorzi, L. Chiecchi, L. Consoli, I. Aprili, P. Guarini, A. Castagna, G.L. Salvagno, C. Pavan, O. Olivieri, NT-proBNP, a useful tool in hypertensive patients undergoing a diagnostic evaluation for primary aldosteronism. Endocrine 45(3), 479–486 (2014). doi:10.1007/s12020-013-0028-6 CrossRefPubMed F. Pizzolo, F. Zorzi, L. Chiecchi, L. Consoli, I. Aprili, P. Guarini, A. Castagna, G.L. Salvagno, C. Pavan, O. Olivieri, NT-proBNP, a useful tool in hypertensive patients undergoing a diagnostic evaluation for primary aldosteronism. Endocrine 45(3), 479–486 (2014). doi:10.​1007/​s12020-013-0028-6 CrossRefPubMed
26.
go back to reference M. Kohno, T. Hanehira, H. Kano, T. Horio, K. Yokokawa, M. Ikeda, M. Minami, K. Yasunari, J. Yoshikawa, Plasma adrenomedullin concentrations in essential hypertension. Hypertension 27(1), 102–107 (1996)CrossRefPubMed M. Kohno, T. Hanehira, H. Kano, T. Horio, K. Yokokawa, M. Ikeda, M. Minami, K. Yasunari, J. Yoshikawa, Plasma adrenomedullin concentrations in essential hypertension. Hypertension 27(1), 102–107 (1996)CrossRefPubMed
27.
go back to reference G.P. Rossi, G. Bernini, G. Desideri, B. Fabris, C. Ferri, G. Giacchetti, C. Letizia, M. Maccario, M. Mannelli, M.J. Matterello, D. Montemurro, G. Palumbo, D. Rizzoni, E. Rossi, A.C. Pessina, F. Mantero, Renal damage in primary aldosteronism: results of the PAPY Study. Hypertension 48(2), 232–238 (2006). doi:10.1161/01.HYP.0000230444.01215.6a CrossRefPubMed G.P. Rossi, G. Bernini, G. Desideri, B. Fabris, C. Ferri, G. Giacchetti, C. Letizia, M. Maccario, M. Mannelli, M.J. Matterello, D. Montemurro, G. Palumbo, D. Rizzoni, E. Rossi, A.C. Pessina, F. Mantero, Renal damage in primary aldosteronism: results of the PAPY Study. Hypertension 48(2), 232–238 (2006). doi:10.​1161/​01.​HYP.​0000230444.​01215.​6a CrossRefPubMed
28.
go back to reference C. Letizia, G. De Toma, S. Cerci, R. Massa, S. Coassin, S. Subioli, L. Scuro, A. De Ciocchis, Adrenomedullin levels are high in primary aldosteronism due to adenoma and decline after surgical cure. Blood Press. 7(1), 19–23 (1998)CrossRefPubMed C. Letizia, G. De Toma, S. Cerci, R. Massa, S. Coassin, S. Subioli, L. Scuro, A. De Ciocchis, Adrenomedullin levels are high in primary aldosteronism due to adenoma and decline after surgical cure. Blood Press. 7(1), 19–23 (1998)CrossRefPubMed
29.
go back to reference C. Letizia, S. Subioli, S. Cerci, C. Caliumi, C. Verrelli, E. Delfini, M. Celi, L. Scuro, E. D’Erasmo, High plasma adrenomedullin concentrations in patients with high-renin essential hypertension. JRAAS 3(2), 126–129 (2002). doi:10.3317/jraas.2002.014 PubMed C. Letizia, S. Subioli, S. Cerci, C. Caliumi, C. Verrelli, E. Delfini, M. Celi, L. Scuro, E. D’Erasmo, High plasma adrenomedullin concentrations in patients with high-renin essential hypertension. JRAAS 3(2), 126–129 (2002). doi:10.​3317/​jraas.​2002.​014 PubMed
30.
go back to reference T. Kita, M. Tokashiki, K. Kitamura, Long-term therapy with nifedipine-CR improves arterio-sclerosis related markers in patients with untreated essential hypertension. Open Hypertens. J. 1(1), 1–6 (2008)CrossRef T. Kita, M. Tokashiki, K. Kitamura, Long-term therapy with nifedipine-CR improves arterio-sclerosis related markers in patients with untreated essential hypertension. Open Hypertens. J. 1(1), 1–6 (2008)CrossRef
Metadata
Title
Pathophysiological functions of adrenomedullin and natriuretic peptides in patients with primary aldosteronism
Authors
Wei Hu
Pang-hu Zhou
Xiao-bin Zhang
Chang-geng Xu
Wei Wang
Publication date
01-03-2015
Publisher
Springer US
Published in
Endocrine / Issue 2/2015
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-014-0316-9

Other articles of this Issue 2/2015

Endocrine 2/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.