Aldosterone augments adrenomedullin production without stimulating pro-adrenomedullin N-terminal 20 peptide secretion in vascular smooth muscle cells.
OBJECTIVE
Both adrenomedullin (AM) and pro-adrenomedullin N-terminal 20 peptide (PAMP), processed from the same precursor of prepro-adrenomedullin (preproAM), have differential biological properties; AM dilates blood vessels and presumably affects the vascular remodeling, while PAMP inhibits catecholamine secretion. Since aldosterone has been shown to be involved in vascular remodeling, we examined the effects of aldosterone on AM and PAMP secretion and preproAM gene expression in human aortic vascular smooth muscle cells (VSMC).


METHODS
AM and PAMP secreted from human VSMC incubated with aldosterone were measured by radioimmunoassay, and preproAM gene expression was evaluated by quantitative polymerase chain reaction.


RESULTS
Cultured human VSMC secreted both AM and PAMP into the media, while the secretion rate of AM was much higher than that of PAMP. Aldosterone increased preproAM gene expression in the cultured VSMC in a dose-dependent fashion following incubation for 48 h, with a concomitant increase in AM secretion from the cells, but PAMP secretion remained unchanged. Aldosterone-stimulated AM secretion was significantly reduced by spironolactone. Reverse-phase high-performance liquid chromatography analyses showed that immunoreactive AM secreted from the VSMC untreated or treated with aldosterone emerged at the point of human AM(1-52)-NH2.


CONCLUSIONS
AM production was stimulated by aldosterone in cultured human VSMC without an increase in PAMP secretion, suggesting a possible role of AM in modulating vascular remodeling by aldosterone.
Uemura
Tomohiko
T
First Department of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan.
Kato
Johji
J
Kuwasako
Kenji
K
Kitamura
Kazuo
K
Kangawa
Kenji
K
Eto
Tanenao
T
D053607:Adrenomedullin; D000450:Aldosterone / Q000494:pharmacology*; D001011:Aorta; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology
D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D011506:Proteins; C112034:preproadrenomedullin; D053607:Adrenomedullin; D013148:Spironolactone; D000450:Aldosterone