Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Nov;94(5):2158–2161. doi: 10.1172/JCI117573

Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure.

T Ishimitsu 1, T Nishikimi 1, Y Saito 1, K Kitamura 1, T Eto 1, K Kangawa 1, H Matsuo 1, T Omae 1, H Matsuoka 1
PMCID: PMC294670  PMID: 7962564

Abstract

Adrenomedullin is a potent hypotensive peptide newly discovered in pheochromocytoma tissue by monitoring its elevating activity on platelet cAMP. We measured plasma concentration of adrenomedullin in patients with essential hypertension and chronic renal failure. As compared with normal subjects, plasma adrenomedullin was increased by 26% (P < 0.05) in hypertensives without organ damage and by 45% (P < 0.005) in those with organ damage. The increase in plasma adrenomedullin was more prominent in renal failure than in hypertension. Renal failure patients with plasma creatinine of 1.5-3, 3-6, and > 6 mg/dl had higher plasma adrenomedullin levels than healthy subjects by 78% (P < 0.05), 131% (P < 0.001), and 214% (P < 0.001), respectively. Moreover, adrenomedullin showed intimate correlations with norepinephrine, atrial natriuretic peptide, and cAMP in plasma (r = 0.625, P < 0.001; r = 0.656, P < 0.001; and r = 0.462, P < 0.001; respectively). Thus, plasma adrenomedullin is supposed to increase in association with changes in sympathetic nervous activity and body fluid volume in hypertension and renal failure. Considering its potent vasodilator effect, adrenomedullin may be involved in the defense mechanism preserving the integrity of the cardiovascular system in these disorders.

Full text

PDF
2158

Images in this article

2159Image
on p.2159

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Evans D. B. Modulation of cAMP: mechanism for positive inotropic action. J Cardiovasc Pharmacol. 1986;8 (Suppl 9):S22–S29. [PubMed] [Google Scholar]
  2. Hirata Y., Ishii M., Fukui K., Hayakawa H., Namba S., Dan Y., Ishimitsu T., Sugimoto T., Kimura K., Matsuoka H. A possible physiological role of atrial natriuretic peptide in body fluid volume regulation. J Cardiovasc Pharmacol. 1989;13 (Suppl 6):S63–S68. [PubMed] [Google Scholar]
  3. Honma M., Satoh T., Takezawa J., Ui M. An ultrasensitive method for the simultaneous determination of cyclic AMP and cyclic GMP in small-volume samples from blood and tissue. Biochem Med. 1977 Dec;18(3):257–273. doi: 10.1016/0006-2944(77)90060-6. [DOI] [PubMed] [Google Scholar]
  4. Ishiyama Y., Kitamura K., Ichiki Y., Nakamura S., Kida O., Kangawa K., Eto T. Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats. Eur J Pharmacol. 1993 Sep 14;241(2-3):271–273. doi: 10.1016/0014-2999(93)90214-3. [DOI] [PubMed] [Google Scholar]
  5. Jaspan J. B., Mako M. E., Kuzuya H., Blix P. M., Horwitz D. L., Rubenstein A. H. Abnormalities in circulating beta cell peptides in chronic renal failure: comparison of C-peptide, proinsulin and insulin. J Clin Endocrinol Metab. 1977 Sep;45(3):441–446. doi: 10.1210/jcem-45-3-441. [DOI] [PubMed] [Google Scholar]
  6. Kitamura K., Ichiki Y., Tanaka M., Kawamoto M., Emura J., Sakakibara S., Kangawa K., Matsuo H., Eto T. Immunoreactive adrenomedullin in human plasma. FEBS Lett. 1994 Mar 21;341(2-3):288–290. doi: 10.1016/0014-5793(94)80474-5. [DOI] [PubMed] [Google Scholar]
  7. Kitamura K., Kangawa K., Kawamoto M., Ichiki Y., Nakamura S., Matsuo H., Eto T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun. 1993 Apr 30;192(2):553–560. doi: 10.1006/bbrc.1993.1451. [DOI] [PubMed] [Google Scholar]
  8. Kitamura K., Sakata J., Kangawa K., Kojima M., Matsuo H., Eto T. Cloning and characterization of cDNA encoding a precursor for human adrenomedullin. Biochem Biophys Res Commun. 1993 Jul 30;194(2):720–725. doi: 10.1006/bbrc.1993.1881. [DOI] [PubMed] [Google Scholar]
  9. Lang R. E., Thölken H., Ganten D., Luft F. C., Ruskoaho H., Unger T. Atrial natriuretic factor--a circulating hormone stimulated by volume loading. Nature. 1985 Mar 21;314(6008):264–266. doi: 10.1038/314264a0. [DOI] [PubMed] [Google Scholar]
  10. Levitzki A. From epinephrine to cyclic AMP. Science. 1988 Aug 12;241(4867):800–806. doi: 10.1126/science.2841758. [DOI] [PubMed] [Google Scholar]
  11. Melick R. A., Martin T. J. Parathyroid hormone metabolism in man: effect of nephrectomy. Clin Sci. 1969 Dec;37(3):667–674. [PubMed] [Google Scholar]
  12. Morgan J. P., Perreault C. L., Morgan K. G. The cellular basis of contraction and relaxation in cardiac and vascular smooth muscle. Am Heart J. 1991 Mar;121(3 Pt 1):961–968. doi: 10.1016/0002-8703(91)90227-9. [DOI] [PubMed] [Google Scholar]
  13. Nuki C., Kawasaki H., Kitamura K., Takenaga M., Kangawa K., Eto T., Wada A. Vasodilator effect of adrenomedullin and calcitonin gene-related peptide receptors in rat mesenteric vascular beds. Biochem Biophys Res Commun. 1993 Oct 15;196(1):245–251. doi: 10.1006/bbrc.1993.2241. [DOI] [PubMed] [Google Scholar]
  14. Oppermann M., Kurts C., Zierz R., Quentin E., Weber M. H., Götze O. Elevated plasma levels of the immunosuppressive complement fragment Ba in renal failure. Kidney Int. 1991 Nov;40(5):939–947. doi: 10.1038/ki.1991.298. [DOI] [PubMed] [Google Scholar]
  15. Salzman E. W. Cyclic AMP and platelet function. N Engl J Med. 1972 Feb 17;286(7):358–363. doi: 10.1056/NEJM197202172860708. [DOI] [PubMed] [Google Scholar]
  16. Sohn H. E., Furukawa Y., Yumita S., Miura R., Yoshinaga K., Yamane R. [Scrutinization of the direct assay method for plasma cyclic AMP and clinical applications of nephrogenous cyclic AMP]. Nihon Naibunpi Gakkai Zasshi. 1985 Sep 20;61(9):912–923. doi: 10.1507/endocrine1927.61.9_912. [DOI] [PubMed] [Google Scholar]
  17. Yamaji T., Ishibashi M., Takaku F. Atrial natriuretic factor in human blood. J Clin Invest. 1985 Oct;76(4):1705–1709. doi: 10.1172/JCI112159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Yasue H., Yoshimura M., Sumida H., Kikuta K., Kugiyama K., Jougasaki M., Ogawa H., Okumura K., Mukoyama M., Nakao K. 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. 1994 Jul;90(1):195–203. doi: 10.1161/01.cir.90.1.195. [DOI] [PubMed] [Google Scholar]
  19. Yoshimura M., Komori T., Nakanishi T., Takahashi H. Estimation of sulphoconjugated catecholamine concentrations in plasma by high-performance liquid chromatography. Ann Clin Biochem. 1993 Mar;30(Pt 2):135–141. doi: 10.1177/000456329303000204. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES