11beta-Hydroxysteroid dehydrogenase in the heart of normotensive and hypertensive rats.
Corticosteroids have been shown to play a role in cardiac remodeling, with the possibility of a direct effect of overexpression of 11beta-hydroxysteroid dehydrogenase (11HSD) isoform 2 at the level of the cardiomyocytes. The aim of this study was to examine cardiac steroid metabolism in hypertensive rats with hearts that are hypertrophied and fibrotic and have structural alterations in the coronary circulation. To assess possible alterations of cardiac steroid metabolism the expression and activity of both isoforms of 11beta-hydroxysteroid dehydrogenase (11HSD) were studied in spontaneously hypertensive rats (SHR), their normotensive controls Wistar-Kyoto (WKY), and in Dahl salt-sensitive (DS) and salt-resistant rats (DR) kept on a low- or high-salt diet. Using real-time quantitative RT-PCR and enzyme activity assay we found strain-dependent differences in cardiac metabolism of glucocorticoids. In Dahl rats expression of 11HSD1 and 11HSD2 mRNA was lower in DS than in DR rats and was not influenced by dietary salt intake; 11HSD1 mRNA was expressed at higher level than 11HSD2 mRNA. NADP(+)-dependent cardiac 11HSD activity showed similar distribution as 11HSD1 mRNA-lower activity in DS than in DR rats and no effect of salt intake. In SHR and WKY strains 11HSD2 mRNA expression was significantly higher in WKY than in SHR but no differences were observed in 11HSD1 mRNA abundance and NADP(+)-dependent 11HSD activity. These results show that the heart is able to metabolize glucocorticoids and that this metabolism is strain-dependent but do not support the notion of association between cardiac hypertrophy and changes of 11HSD1 and 11HSD2 expression.
Mazancová
Karla
K
Institute of Physiology, Czech Academy of Sciences, Vídenská 1083, 142 20 Prague 4 Krc, Czech Republic.
Kopecký
Martin
M
Miksík
Ivan
I
Pácha
Jirí
J
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology; D004039:Diet, Sodium-Restricted; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000378:metabolism; D006973:Hypertension / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012016:Reference Values
D005938:Glucocorticoids; D012333:RNA, Messenger; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1