title: Chronic intermittent hypoxia induces 11beta-hydroxysteroid dehydrogenase in rat heart.
abstract: Corticosteroids are known to not only regulate electrolyte homeostasis but also play a role in the cardiovascular system, including myocardial remodeling. Because transgenic mice that overexpress 11beta-hydroxysteroid dehydrogenase (11HSD) type 2 in cardiomyocytes have been shown to spontaneously develop cardiac hypertrophy and fibrosis, we investigated whether changes in the cardiac metabolism of glucocorticoids accompany remodeling of the heart under physiological conditions. In the present study, glucocorticoid metabolism and 11HSD2 were explored in the hearts of rats exposed to chronic intermittent hypobaric hypoxia (CIH), which induces hypertrophy and fibrosis of the right and less of the left ventricle. We first demonstrated that adaptation to CIH led to a significant increase in 11HSD2 transcript levels and activity in the myocardium. In contrast, neither 11HSD1 activity and mRNA level nor the abundance of mineralocorticoid and glucocorticoid receptor mRNA were up-regulated. The adaptation to CIH also led to an increase of 11HSD2 mRNA in isolated cardiomyocytes, whereas 11HSD1, glucocorticoid receptor, and mineralocorticoid receptor mRNA levels were not changed in comparison with the cardiomyocytes of control normoxic rats. The changes in cardiac metabolism of glucocorticoids were accompanied by inflammatory responses. The expression levels of the proinflammatory markers cyclooxygenase-2 and osteopontin were significantly increased in both the myocardium and the cardiomyocytes isolated from rats exposed to CIH. These findings suggest that myocardial remodeling induced by CIH is associated with the up-regulation of cardiac 11HSD2. Consequently, local metabolism of glucocorticoids could indeed play a role in cardiac hypertrophy and fibrosis.
authors.affiliation: Institute of Physiology, Czech Academy of Sciences, 142 20 Prague 4, Krc, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Klusonová
authors.forename: Lenka
authors.initials: L
authors.lastname: Reháková
authors.forename: Gudrun
authors.initials: G
authors.lastname: Borchert
authors.forename: Karla
authors.initials: K
authors.lastname: Vagnerová
authors.forename: Jan
authors.initials: J
authors.lastname: Neckár
authors.forename: Peter
authors.initials: P
authors.lastname: Ergang
authors.forename: Ivan
authors.initials: I
authors.lastname: Miksík
authors.forename: Frantisek
authors.initials: F
authors.lastname: Kolár
authors.forename: Jirí
authors.initials: J
authors.lastname: Pácha
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000096:biosynthesis; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000096:biosynthesis*; D000450:Aldosterone / Q000097:blood; D000818:Animals; D006332:Cardiomegaly; D003345:Corticosterone / Q000097:blood; D005355:Fibrosis; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003345:Corticosterone