The possible roles of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in cardiac fibrosis in the spontaneously hypertensive rat.
In hypertension, aldosterone has been demonstrated to play a crucial role in cardiac fibrosis, which generally increases cardiac morbidity and death. However, few studies have reported the expression of the mineralocorticoid receptor (MR) and 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in the heart under hypertensive conditions. Therefore, in this study, spontaneously hypertensive rats (SHR) were examined to elucidate the possible actions of mineralocorticoids via binding to MR. Wister Kyoto Rat (WKY), SHR, stroke-prone SHR (SHRSP), and malignant SHRSP (M-SHRSP) were used. Total RNA was extracted from the left ventricle of these rats, and examined for the expression levels of MR, 11beta-HSD2 and Collagen types 1 and 3 using reverse transcription real-time quantitative polymerase chain reaction employing the Light Cycler Instrument. Blood pressure was significantly different among each group. The mean mRNA levels for MR, 11beta-HSD2 and Collagen types 1 and 3 in M-SHRSP were found to be significantly increased compared to those of WKY, whereas no significant differences in mRNA levels were detected among SHR and SHRSP. Findings from the present study appear to demonstrate that MR and 11beta-HSD2 mRNA significantly rise in the left ventricle of M-SHRSP and increase of these mRNA is one of the cause of cardiac fibrosis.
Konishi
Akinobu
A
Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8575, Japan. akonishi@mail.cc.tohoku.ac.jp
Tazawa
Chika
C
Miki
Yasuhiro
Y
Darnel
Andrew D
AD
Suzuki
Takashi
T
Ohta
Yoshio
Y
Suzuki
Tsuneyuki
T
Tabayashi
Koichi
K
Sasano
Hironobu
H
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D001483:Base Sequence; D009202:Cardiomyopathies / Q000235:genetics / Q000503:physiopathology*; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D013045:Species Specificity
D024042:Collagen Type I; D024061:Collagen Type III; D017931:DNA Primers; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases