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Glucocorticoids play important roles in development and 'fetal programming'. Fetal exposure to excess glucocorticoids reduces birth weight and causes later hypertension. To investigate these processes further we have determined the detailed category of 11 beta-hydroxysteroid dehydrogenase type2 (11 beta-HSD2, which potently inactivates glucocorticoids) and(More)
11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) intracellularly regenerates active corticosterone from circulating inert 11-dehydrocorticosterone (11-DHC) in specific tissues. The hippocampus is a brain structure particularly vulnerable to glucocorticoid neurotoxicity with aging. In intact hippocampal cells in culture, 11beta-HSD-1 acts as a(More)
Deficiency of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in humans leads to the syndrome of apparent mineralocorticoid excess (SAME), in which cortisol illicitly occupies mineralocorticoid receptors, causing sodium retention, hypokalemia, and hypertension. However, the disorder is usually incompletely corrected by suppression of cortisol,(More)
11beta-Hydroxysteroid dehydrogenases (11beta-HSDs) catalyze interconversion of active corticosterone and inert 11-dehydrocorticosterone, thus regulating glucocorticoid access to intracellular receptors in vivo. 11beta-HSD type 1 is a reductase, locally regenerating active glucocorticoids. To explore the role of this isozyme in the brain, we examined(More)
Essential hypertension is a common human disease believed to result from the interplay of multiple genetic and environmental determinants. In genetic studies of two large panels of hypertensive sibships from widely separated geographical areas, we obtained evidence of genetic linkage between the angiotensinogen gene (AGT) and hypertension, demonstrated(More)
Glucocorticoid hormones, acting via nuclear receptors, regulate many metabolic processes, including hepatic gluconeogenesis. It recently has been recognized that intracellular glucocorticoid concentrations are determined not only by plasma hormone levels, but also by intracellular 11beta-hydroxysteroid dehydrogenases (11beta-HSDs), which interconvert active(More)
A novel inbred rat model with inducible hypertension has been generated using a renin transgene under the transcriptional control of the cytochrome P450, Cyp1a1 promoter. The degree and duration of hypertension are regulated tightly by administration of the natural xenobiotic indole-3 carbinol and can be readily reversed. Induction experiments reveal(More)
BACKGROUND Genetic background has a major influence on the manifestation of multifactorial diseases such as hypertension in which severe complications may be caused through an interaction with additional factors, which may be genetically determined. We have previously described a genetic model of malignant hypertension (MH) in rats carrying the mouse Ren2(More)
Atherosclerosis is a chronic inflammatory disease affecting arterial vessels. Strategies to reduce the inflammatory responses of endothelial cells and macrophages may slow lesion development and prevent complications such as plaque rupture. The human protease human neutrophil elastase (HNE), oxidized low density lipoprotein, LPS, and TNF-alpha were chosen(More)
During the last two decades numerous research teams demonstrated that skeletal muscles function as an exercise-dependent endocrine organ secreting dozens of myokines. Variety of physiological and pathophysiological implications of skeletal muscle myokines secretion has been described; however, upstream signals and sensing mechanisms underlying this(More)