PMID- 17587755
OWN - NLM
STAT- MEDLINE
DCOM- 20070718
LR  - 20131121
IS  - 0916-9636 (Print)
IS  - 0916-9636 (Linking)
VI  - 30
IP  - 5
DP  - 2007 May
TI  - Spironolactone modulates expressions of cardiac mineralocorticoid receptor and 
      11beta-hydroxysteroid dehydrogenase 2 and prevents ventricular remodeling in 
      post-infarct rat hearts.
PG  - 427-37
AB  - Aldosterone antagonists have been reported to prevent ventricular remodeling 
      after myocardial infarction (MI) via their action to extracellular matrix (ECM). 
      However, it remains largely unknown whether aldosterone antagonists attenuate 
      myocyte loss in the remodeling process. The present study examined whether 
      spironolactone prevents myocyte apoptosis and improves post-infarct ventricular 
      remodeling in rats. MI was achieved by permanent occlusion of the left coronary 
      artery. Administration of spironolactone (100 mg/kg/day) was started immediately 
      after MI. Sprague-Dawley rats were divided into four groups: 1) sham, 2) 
      spironolactone-treated sham, 3) untreated MI, 4) spironolactone-treated MI. 
      Echocardiographic parameters (left ventricular [LV] diastolic dimension [LVDd], 
      fractional shortening [%FS]), hemodynamic parameters (LV systolic pressure 
      [LVSP], LV end-diastolic pressure [LVEDP], dP/dt(max) and dP/dt(min)) and 
      collagen accumulation quantitated by Masson's Trichrome staining were 
      significantly improved in the spironolactone-treated MI group on the 14th day, 
      compared with the untreated MI group. Moreover, the percentage of apoptotic 
      myocytes evaluated by terminal deoxynucleotide transferase-mediated dUTP nick end 
      labeling (TUNEL) assay was significantly lower in the spironolactone-treated MI 
      group on the 2nd (3.54% vs. 5.79% in untreated MI group), 7th (0.65% vs. 1.37% in 
      untreated MI group) and 14th days (0.11% vs. 0.16% in untreated MI group). Real 
      time reverse transcription-polymerase chain reaction (RT-PCR) analysis showed 
      that the expression of mineralocorticoid receptor (MR) mRNA and that of 
      11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) mRNA, which is known to 
      confer aldosterone selectivity on MR, were upregulated in the untreated MI group, 
      and that spironolactone significantly suppressed the expression of these genes. 
      Moreover, spironolactone significantly inhibited aldosterone-induced apoptosis in 
      cultured rat cardiac myocytes in a dose-dependent fashion. Our study demonstrates 
      that, in addition to their effect on ECM, aldosterone antagonists inhibit myocyte 
      apoptosis and prevent post-infarct ventricular remodeling by modulating the 
      expression levels of MR and 11beta-HSD2, which are enhanced in the remodeling 
      heart.
FAU - Takeda, Mitsuo
AU  - Takeda M
AD  - Department of Cardiovascular Medicine, Kyoto Prefectural University School of 
      Medicine, Kyoto, Japan.
FAU - Tatsumi, Tetsuya
AU  - Tatsumi T
FAU - Matsunaga, Shinsaku
AU  - Matsunaga S
FAU - Hayashi, Hironori
AU  - Hayashi H
FAU - Kimata, Masaki
AU  - Kimata M
FAU - Honsho, Shoken
AU  - Honsho S
FAU - Nishikawa, Susumu
AU  - Nishikawa S
FAU - Mano, Akiko
AU  - Mano A
FAU - Shiraishi, Jun
AU  - Shiraishi J
FAU - Yamada, Hiroyuki
AU  - Yamada H
FAU - Takahashi, Tomosaburo
AU  - Takahashi T
FAU - Matoba, Satoaki
AU  - Matoba S
FAU - Kobara, Miyuki
AU  - Kobara M
FAU - Matsubara, Hiroaki
AU  - Matsubara H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - 27O7W4T232 (Spironolactone)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenase Type 2/*genetics/metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Blood Pressure/drug effects
MH  - Cells, Cultured
MH  - Fibrosis
MH  - Gene Expression Regulation/drug effects
MH  - Heart Rate/drug effects
MH  - Male
MH  - Mineralocorticoid Receptor Antagonists/*pharmacology
MH  - Myocardial Infarction/*drug therapy/pathology/physiopathology
MH  - Myocardium/enzymology/pathology
MH  - Myocytes, Cardiac/drug effects/enzymology/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Mineralocorticoid/*genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Spironolactone/*pharmacology
MH  - Survival Rate
MH  - Ventricular Remodeling/*drug effects
EDAT- 2007/06/26 09:00
MHDA- 2007/07/19 09:00
CRDT- 2007/06/26 09:00
PHST- 2007/06/26 09:00 [pubmed]
PHST- 2007/07/19 09:00 [medline]
PHST- 2007/06/26 09:00 [entrez]
AID - JST.JSTAGE/hypres/30.427 [pii]
AID - 10.1291/hypres.30.427 [doi]
PST - ppublish
SO  - Hypertens Res. 2007 May;30(5):427-37. doi: 10.1291/hypres.30.427.