Mineralocorticoid receptor is overexpressed in cardiomyocytes of patients with congestive heart failure.
Mineralocorticoid receptors (MRs) have been identified in the human cardiovascular tissues. We determined MR expression in the failing heart to clarify the mechanism of action of aldosterone antagonist in the treatment of congestive heart failure. MR protein and MR mRNA content were detected by immunohistochemical staining and in situ hybridization in the cardiac tissues. Immunohistochemical staining of the receptor, as well as in situ hybridization of MR mRNA, was dense in cardiomyocytes of the failing left ventricle as compared with the controls. The staining ratio of the cytoplasm to the interstitium showed that MRs were located mainly in the cytoplasm. The cytoplasm to the interstitium in the failing left ventricle was 1.53+/-0.13, which was significantly higher than that of the controls 1.25+/-0.19 (p<0.05). These findings suggest that the efficacy of aldosterone antagonists in treating congestive heart failure may be in part through blocking the MRs, which are upregulated in the failing heart.
Yoshida
Masahiro
M
Third Department of Internal Medicine, Faculty of Medicine, Fukui, Shimoaituski 23, Yoshida-gun, Matsuoka-cho, Fukui 910-1193 Japan.
Ma
Jun
J
Tomita
Tsutomu
T
Morikawa
Norihiro
N
Tanaka
Nobuyoshi
N
Masamura
Katsuhiko
K
Kawai
Yasuyuki
Y
Miyamori
Isamu
I
D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D032383:Myocytes, Cardiac / Q000378:metabolism*; D005996:Nitroglycerin / Q000627:therapeutic use; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013148:Spironolactone / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D005996:Nitroglycerin