Horm Metab Res 2005; 37(5): 281-285
DOI: 10.1055/s-2005-861471
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Angiotensin II Stimulates Cardiac Adrenomedullin Production and Causes Accumulation of Mature Adrenomedullin Independently of Hemodynamic Stress in Vivo

H.  Onitsuka1 , T.  Imamura1 , J.  Yamaga1 , K.  Kuwasako1 , K.  Kitamura1 , T.  Eto1
  • 1 First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan
Further Information

Publication History

Received 19 July 2004

Accepted after revision 4 October 2004

Publication Date:
22 June 2005 (online)

Abstract

Adrenomedullin is a potent hypotensive peptide that may act on myocytes to inhibit hypertrophy and on fibroblasts to inhibit growth in vitro induced by mechanical stretching and angiotensin II. Adrenomedullin is processed from the inactive intermediate adrenomedullin precursor with a glycine extension, which is subsequently converted to biologically active mature adrenomedullin by enzymatic amidation. Total adrenomedullin is the sum of intermediate and mature adrenomedullin. We examined the effect of a subpressor dose of angiotensin II on the production of left ventricular adrenomedullin and on protein levels of mature adrenomedullin in the left ventricle in vivo. We also investigated whether the effect is mediated by the angiotensin II type 1 receptor. Concentrations of total and mature adrenomedullin in the left ventricle and mature adrenomedullin-to-intermediate adrenomedullin ratio were significantly increased by angiotensin II infusion, regardless of pressure overload. Total and mature adrenomedullin concentrations significantly correlated with the weight of the left ventricle. Furthermore, increased adrenomedullin gene expression and protein levels were completely suppressed by a subdepressor dose of angiotensin II type 1 receptor blocker. In conclusion, angiotensin II stimulates the production of cardiac adrenomedullin and accumulates mature adrenomedullin in the left ventricle independently of hemodynamic stress. These processes are partially regulated through the angiotensin II type 1 receptor in vivo.

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Takuroh Imamura, M. D.

First Department of Internal Medicine · Miyazaki Medical College · University of Miyazaki

Kihara 5200 · Kiyotake · Miyazaki 889-1692 · Japan

Phone: 81-985-85-0872 ·

Fax: 81-985-85-6596

Email: imatak@med.miyazaki-u.ac.jp