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 .
Key words
Amidation - Angiotensin II type 1 receptor - Hypertrophy - Pressure overload - Renin-angiotensin
system
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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